Metastasis is a complicated multistage process that requires the coordination of multiple genes, including both metastasis stimulating genes and metastasis suppressor genes (22) . Genomic instability is one of the driving forces for tumor progression and metastasis development. Among all genetic alterations, inactivation of metastasis suppressor genes is one important factor contributing to the formation of tumor metastasis. Chromosome 11, in particular 11p, is one of the most common regions undergoing genetic alterations in human breast cancer (3, 4, 5) . A previous study demonstrated that a breast cancer metastasis gene or genes exists on chromosome 11 by the fact that the introduction of a normal copy of chromosome 11 into malignant breast cancer cells significantly suppressed their metastatic ability (6) .. The KAI1 gene, located on human chromosome 11p11.2, was initially identified as a metastasis suppressor gene for human prostate cancer (7) . Down-regulation of the KAI1 protein was ...
TY - JOUR. T1 - Adhesion Characteristics of Murine Metastatic and Nonmetastatic Tumor Cells in Vitro. AU - Murray, J. Clifford. AU - Liotta, Lance. AU - Rennard, Stephen I.. AU - Martin, George R.. PY - 1980/2/1. Y1 - 1980/2/1. N2 - We have studied the attachment of mouse fibroblasts, transformed nonmetastatic fibroblasts, and metastatic fibrosarcoma cells to various substrates. The metastatic cells attach preferentially to type IV (basement membrane) collagen in the absence of serum, compared to type I collagen and plastic. In the presence of fibronectin, these cells attach well to both type I and type IV collagens. The normal and transformed fibroblasts attach to all these substrates, although the transformed fibroblasts attach more slowly. The ability to attach to type I collagen and plastic is correlated with the levels of fibronectin and collagen produced by these cells. The data indicate that the transformed and metastatic cells differ from normal cells in their attachment properties and ...
The purpose of these studies was to determine whether hematogenous clonal pulmonary melanoma metastases originate from the expansion of a single cell and if so, by extrapolation, metastasis can be considered a cloning process. Three different cell lines of murine K-1735 melanoma with different metastatic properties and unique karyotypes were injected i.v. into syngeneic C3H/HeN mice as multicell aggregates of individual cell lines or combinations of cell lines. Resultant solitary lung metastases were isolated in culture as individual lines and then karyotyped. Even when heterogeneous clumps of tumor cells were injected, the individual metastases exhibited a karyotype unique to one metastatic cell type. Furthermore, when cellular aggregates were composed of metastatic cells admixed with cells that were tumorigenic but nonmetastatic, the resultant metastases exhibited only the karyotype of the metastatic cells. This finding suggests that the presence of metastatic cells did not change the ...
A new study with mice shows that the fight or flight response to stress can promote breast cancer metastasis to the bone.. Researchers at the Vanderbilt University Center for Bone Biology demonstrated in mice that activation of the sympathetic nervous system - the fight-or-flight response to stress - primes the bone environment for breast cancer cell metastasis. The researchers were able to prevent breast cancer cell lesions in bone using propranolol, a cardiovascular medicine that inhibits sympathetic nervous system signals.. Metastasis - the spread of cancer cells to organs and bone - is more likely to kill patients than a primary breast tumor, said Florent Elefteriou, Ph.D., director of the Vanderbilt Center for Bone Biology.. Preventing metastasis is really the goal we want to achieve, he said.. Elefteriou and his colleagues learned in previous studies that the sympathetic nervous system stimulated bone remodeling, and that it used some of the same signaling molecules that have been ...
We have developed a robust approach for imaging of BCSC growth and dissemination, which permits both macroscopic and microscopic analysis of cancer progression. In our studies, the imaging assays facilitated development of visible human-in-mouse xenograft tumor models with spontaneous metastases to lungs or local/distant lymph nodes. Our patient-tumor derived xenograft models will be able to overcome some limitations of previous metastatic models with human cancer cell lines or mouse tumor models. Spontaneous metastases present representative features of patient tumors that can be used in predictive models of metastasis and therapeutic response, but cannot be recapitulated by lung/bone colonization models via tail-vein or intracardiac injections. This point is driven home by the observation that these xenografts metastasize to the lungs but not the bones when grown in the mammary fat pads. This likely reflects that triple-negative ER− breast cancers tend to metastasize to the lungs rather ...
Cancer cell metastasis is one of the most critical steps in tumor development and is responsible for more than 80 of cancer related deaths. Among the molecules involved in promoting cancer metastasis, the role of the cell adhesion molecules, CD44 and CD146 are well known in promoting cancer cell motility and metastasis. Despite this knowledge, the molecular mechanism through which CD44 promotes tumor development and cell metastasis is still nascent. CD146 (MUC 18) was, first identified in highly metastatic melanomas. The absence of CD146 in normal melanocytes and its high expression in melanomas suggests its tumor promoting actions. Despite the association between CD146 expression and development of melanoma, its expression patterns and role in normal and metastatic breast tissues still remains controversial. This study aims to elucidate some of these discrepancies by presenting CD146 as a downstream target for CD44, in a way such that CD146 expression is related to CD44 and regulates the tumor ...
Tumor cell metastasis and proliferation are crucial for tumor development and result in loss of life of tumor individuals. TLR4 signaling pathway. It offers fresh insights for the systems of tumor advancement and metastasis, and suggests targeting TLR4 and OPN as an intervention in the ovarian cancer treatment. proliferation activity of tumor cells. Without LPS stimulation, the proliferation activity of tumor cells increased during 12 h. The cell proliferation significantly changed by LPS stimulation, and the maximum absorbance value at 429 nm was present after 6 h, with a proliferation rate of approximately 137.1% compared to cells without stimulation (Figure 2AC2B). To investigate the effect of TLR4 signal block on cell proliferation, the TLR4 inhibitor TAK-242 was used. The LPS-stimulated increase in the proliferation of tumor cells was significantly reduced with TAK-242 pretreatment, whereas no significant change was observed in cells treated with TAK-242 alone (Figure ?(Figure2C).2C). These ...
TY - JOUR. T1 - Homeoprotein Six2 promotes breast cancer metastasis via transcriptional and epigenetic control of E-cadherin expression. AU - Wang, Chu An. AU - Drasin, David. AU - Pham, Catherine. AU - Jedlicka, Paul. AU - Zaberezhnyy, Vadym. AU - Guney, Michelle. AU - Li, Howard. AU - Nemenoff, Raphael. AU - Costello, James C.. AU - Tan, Aik Choon. AU - Ford, Heide L.. PY - 2014/12/15. Y1 - 2014/12/15. N2 - Misexpression of developmental transcription factors occurs often in human cancers, where embryonic programs may be reinstated in a context that promotes or sustains malignant development. In this study, we report the involvement of the kidney development transcription factor Six2 in the metastatic progression of human breast cancer. We found that Six2 promoted breast cancer metastasis by a novel mechanism involving both transcriptional and epigenetic regulation of E-cadherin. Downregulation of E-cadherin by Six2 was necessary for its ability to increase soft agar growth and in vivo ...
Most cancer deaths are due to spreading of the primary tumor to one or several secondary sites, in a process called metastasis. These metastases are often more difficult to treat than the primary tumor and their presence marks severe progression of the disease. Tumor cell metastasis involves cell migration through heterogenous microenvironments in tissues, along anatomical features such as blood vessels and nerves, and into and out of vasculature. Mounting evidence has accumulated, demonstrating that metastatic tumor cells can migrate via several modes or mechanisms of migration, and can switch between these modes depending on the specific features of the microenvironment. Our research in this area is focused on understanding how distinct physical and biochemical cues from the tumor cells microenvironment affect the phenotype, biological signaling, mechanical properties, and interactions with other cells during metastasis. We are interested in metastasis to the brain, which is especially ...
TY - JOUR. T1 - Biopsy of breast cancer metastases. T2 - BMC Cancer. AU - Shachar,Shlomit Strulov. AU - Mashiach,Tanya. AU - Fried,Georgeta. AU - Drumea,Karen. AU - Shafran,Noa. AU - Muss,Hyman B.. AU - Bar-Sela,Gil. PY - 2017/1/4. Y1 - 2017/1/4. N2 - Background: Discordance in hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) status between primary tumors and metastatic sites for breast cancer is well established. However, it is uncertain which patient-related factors lead to biopsy when metastases are suspected and whether having a biopsy impacts survival. Methods: The medical charts of metastatic breast cancer (MBC) patients diagnosed January 2000-August 2014 were retrospectively reviewed. A biopsy was defined as a procedure where tissue was obtained and assessed for both HR and HER2. Both bivariate and multivariate analyses were performed to assess patient characteristics related to biopsy and whether having a biopsy was associated with improved survival. Results: Of ...
Liver is the organ responsible for hematopoiesis during fetal life, which is also a target organ of metastasis for several cancers. In order to recognize the hepatic metastatic changes, obtain a...
Quantitative multiplex reverse transcriptase-polymerase chain reaction was developed for the simultaneous detection of multiple-gene expression levels of formalin-fixed, paraffin-embedded breast cancer samples. Candidate genes were selected from previous microarray data relevant to breast cancer markers that had the potential to serve as predictive markers for metastatic risk. This multiplex gene set included 11 candidate and 3 housekeeping genes, and the aim was to predict breast cancer progression based on lymph node involvement status.
We report a comprehensive analysis of breast cancer metastases by analyzing the full spectrum of metastatic lesions derived from 10 patients who died of metastatic breast cancer and underwent rapid autopsy. By comparing the primary neoplasms from these patients with their metastases and by comparing metastases from one site to another, we identified marked heterogeneity among breast cancer metastases, as well as markers which remained consistent among these lesions. Our results expand the existing body of knowledge regarding breast cancer metastases and have both biological and therapeutic implications.. With regard to distribution of metastases, we confirm the liver, bone, and lung as the most frequent sites of hematogenous dissemination. We also confirm the striking tendency of lobular carcinoma to metastasize to the gastrointestinal tract, as illustrated by cases MBC1 and MBC5. Case MBC5 is particularly instructive, as the invasive ductal carcinoma primary lost E-cadherin expression in most ...
We have investigated the antitumor effects of synthetic MMP inhibitor MMI270 against postoperative lung metastasis from colon cancer in nude rat. The KM12SM human colon cancer cells were injected into the cecal wall, and at 5 weeks after the injection, the cecum was removed including the tumor. Then, 30 mg/kg of MMI270 was administered perorally twice per day for 2 or 4 weeks, either immediately after removal or after week 2 after the removal. At week 7 after the removal, lung metastasis was significantly inhibited by the early administration of MMI270 immediately after the tumor removal but not by the late administration. The survival rates were significantly higher in the rats treated by early administration of MMI270 compared to the survival rate in untreated rats. Moreover, no lung metastasis was detected in some rats with 24-weeks survival treated by early administration. Lower microvessel density, lower PCNA Index and higher Apoptotic Index in the lung metastases of the rats treated with MMI270
UNLABELLED: Metastatic spread of cancer cells to the brain is associated with high mortality, primarily because current diagnostic tools identify only well-advanced metastases. Brain metastases have been shown to induce a robust glial response, including both astrocyte and microglial activation. On the basis of these findings, we hypothesized that this stromal response may provide a sensitive biomarker of tumor burden, in particular through the use of SPECT/PET imaging agents targeting the translocator protein (TSPO) that is upregulated on activated glia. Our goals, therefore, were first to determine the spatial and temporal profile of glial activation during early metastasis growth in vivo and second to assess the potential of the radiolabeled TSPO ligand (123)I-DPA-713 for early detection of brain metastases. METHODS: Metastatic mouse mammary carcinoma 4T1-green fluorescent protein cells were injected either intracerebrally or intracardially into female BALB/c mice to induce brain metastases.
Breast cancer cells with stem cell properties are key contributors to metastatic disease, and there remains a need to better understand and target these cells in human cancers. Here, we identified rare stem-like cells in patients tumors characterized by low levels of the proapoptotic molecule p53-upregulated modulator of apoptosis (PUMA) and showed that these cells play a critical role in tumor progression that is independent of clinical subtype. A signaling axis consisting of the integrin αvβ3, Src kinase, and the transcription factor Slug suppresses PUMA in these cells, promoting tumor stemness. We showed that genetic or pharmacological disruption of αvβ3/Src signaling drives PUMA expression, specifically depleting these stem-like tumor cells; increases their sensitivity to apoptosis; and reduces pulmonary metastasis, with no effect on primary tumor growth. Taken together, these findings point to PUMA as a key vulnerability of stem-like cells and suggest that pharmacological upregulation ...
Breast cancer cells with stem cell properties are key contributors to metastatic disease, and there remains a need to better understand and target these cells in human cancers. Here, we identified rare stem-like cells in patients tumors characterized by low levels of the proapoptotic molecule p53-upregulated modulator of apoptosis (PUMA) and showed that these cells play a critical role in tumor progression that is independent of clinical subtype. A signaling axis consisting of the integrin αvβ3, Src kinase, and the transcription factor Slug suppresses PUMA in these cells, promoting tumor stemness. We showed that genetic or pharmacological disruption of αvβ3/Src signaling drives PUMA expression, specifically depleting these stem-like tumor cells; increases their sensitivity to apoptosis; and reduces pulmonary metastasis, with no effect on primary tumor growth. Taken together, these findings point to PUMA as a key vulnerability of stem-like cells and suggest that pharmacological upregulation ...
The number of clinicians whose eyes glaze over as metastasis researchers dutifully recite the many steps of the metastatic process, and go on to examine tumor cell invasion in minute detail, signals either that we give boring lectures or that we have evoked the so what? response. Those who would favor the latter response might state that, even for the greater than 90% of patients without detectable distant metastases at surgery, it remains possible that tumor cells have already invaded out of the primary tumor and are sitting contentedly in distant sites undetected. Only growth and angiogenesis remain. Why study metastasis when it may be virtually complete by the time the patient walks into the clinic? Has the barn door been left open? Should we all drop our experiments and switch to antiangiogenesis projects?. Two reviews in this series have addressed this critical question, and arrived at similar answers. Investigators from Dr Ann Chambers laboratory have watched it all happen. She and ...
Cancer is a disease of cell growth, but most tumors only become lethal once they metastasize or spread from their first location to sites throughout the body. For the first time, researchers at Thomas Jefferson University in Philadelphia report a single molecule that appears to be the central regulator driving metastasis in prostate cancer. The study, published online July 13th in Cancer Cell, offers a target for the development of a drug that could prevent metastasis in prostate cancer, and possibly other cancers as well.. Finding a way to halt or prevent cancer metastasis has proven elusive. We discovered that a molecule called DNA-PKcs could give us a means of knocking out major pathways that control metastasis before it begins, says Karen Knudsen, Ph.D., Director of the Sidney Kimmel Cancer Center at Thomas Jefferson University, the Hilary Koprowski Professor and Chair of Cancer Biology, Professor of Urology, Radiation Oncology, and Medical Oncology at Jefferson.. Metastasis is thought of ...
Breast cancer (BCa) remains as the second leading cause of cancer-related death in women worldwide. The majority of the deaths are due to its progression to metastatic BCa. Although Grb2-associated binding protein 1 (Gab1) has been implicated in tumor proliferation and metastasis in multiple tumors including colorectal cancer, hepatocellular carcinoma and ovarian cancer, whether and how it regulates BCa metastasis are still poorly understood. Western blot assay and immunohistochemical (IHC) staining were performed to assess expression of Gab1 in primary and metastatic BCa clinical samples. Biological function assay studies in vitro and in vivo were employed to investigate the functions of Gab1 during BCa metastasis. Co-immunoprecipitation (co-IP) assessment, western blot assay and immunofluorescence (IF) staining were carried out to investigate the underlying mechanism for the function of Gab1 on BCa metastasis. In this study, we found that expression level of Gab1 was increased significantly in BCa
SENP3 promotes gastric cancer cell metastasis in vivo(A) The efficiency of SENP3 overexpression in SGC7901-SENP3 cells used for tumorigenesis in nude mice. (B)
Background Metastasis is the most frequent cause of treatment failure and death in colorectal cancer. Early detection of tumors and metastases is crucial for improving treatment strategies and patient outcome. Development of reliable biomarkers and simple tests routinely applicable in the clinic for detection, prognostication, and therapy monitoring is of special interest. We recently identified the novel gene Metastasis-Associated in Colon Cancer 1 (MACC1), a key regulator of the HGF/Met-pathway. MACC1 is a strong prognostic biomarker for colon cancer metastasis and allows identification of high-risk subjects in early stages, when determined in patients primary tumors. To overcome the limitation of a restricted number of molecular analyses in tumor tissue, the establishment of a non-invasive blood test for early identification of high-risk cancer patients, for monitoring disease course and therapy response is strongly needed. Methodology/Principal Findings For the first time, we describe a non
Previously, we showed that a chemokine CCL2 recruits IMs to metastatic sites where they differentiate to MAMs (Qian et al., 2011). In this study, we revealed a novel role for CCL2 as a trigger of a prometastatic chemokine cascade involving CCL3 signaling via CCR1 that is required for efficient metastasis. These data illustrate a signaling relay that amplifies the pathology already in the system by promoting retention of recruited monocytes that stimulate tumor cell establishment at the metastatic site.. Our in vivo and in vitro results indicate that CCL2 can increase CCL3 expression in MAMs at the metastasis site. The CCL2-induced CCL3 expression is likely to be specific to the prometastatic macrophage lineage, as neutralization of CCL2 by antibodies significantly reduced Ccl3 expression in IMs and MAMs, but not in resident monocytes or macrophages. Consistent with this interpretation, expression of Ccl3 was highest in MAMs compared with other leukocytes in the tumor-bearing lung. Importantly, a ...
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Gastric cancer (GC) is one of the common reasons of cancer-related death with few biomarkers for diagnosis and prognosis. Solute carrier family 2 (facilitated glucose transporter) member 1 protein SLC2A1, also known as glucose transporter type 1 (GLUT1), has been associated with tumor progression, metastasis, and poor prognosis in many human solid tumors. However, little is reported about its clinical significance and biological functions in GC. Here we observed a strong up-regulation of SLC2A1 in patients with GC and found that SLC2A1 was significantly correlated with depth of invasion and clinical stage. Additionally, over-expression of SLC2A1 in GC cells promotes cellular proliferation and metastasis in vitro and enhances tumor growth in vivo as well as enhancement of glucose utilization. Meanwhile, elevated SLC2A1 also contributes to tumor metastasis in vitro. Our results indicate SLC2A1 exhibits a pivotal role in tumor growth, metastasis and glucose metabolism, and also suggest SLC2A1 as a
Metastatic disease is the leading cause of death among cancer patients and involves a complex and inefficient process. Every step of the metastatic process can be rate limiting and is influenced by non-malignant host cells interacting with the tumor cell. Over a century ago, experiments first indicated a link between the immune system and metastasis. This phenomenon, called concomitant immunity, indicates that the primary tumor induces an immune response, which may not be sufficient to destroy the primary tumor, but prevents the growth of a secondary tumor or metastases. Since that time, many different immune cells have been shown to play a role in both inhibiting and promoting metastatic disease. Here we review classic and new observations, describing the links between the immune system and metastasis that inform the development of cancer therapies.
A role for bone marrow-derived cells (BMDCs) in promoting metastatic tumor growth is emerging, with important implications for therapeutic strategies to decrease tumor metastases. While previous work has shown accumulation of CD11b+ BMDCs in the lungs of mice bearing metastatic breast tumors, questions remain about the precise identity of these cells, the factors that regulate CD11b+ cell accumulation, and the potential long-term influence of CD11b+ cells on metastatic growth. We used transplantable (4T1, 4TO7, 67NR) and spontaneous (polyomavirus middle-T; PyVmT) mammary tumor models to study the identity, induction, longevity, and function of CD11b+ BMDCs in tissues. Using flow cytometry and ex vivo immune suppression assays, we established that metastatic mammary tumors induce splenic expansion and pulmonary accumulation of functional CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs) and CD11b+F4/80+ macrophages (Mϕs). MDSCs suppress T cell-mediated immune responses against tumor cells and ...
Next, they found that the Skp2 overexpression also results in more RhoA, and that both Skp2 and Myc were required for the metastasis-producing RhoA to be overexpressed. This cancer-promoting pathway is the second way Skp2 fuels cancer growth, Lin said. Skp2 has been shown to work through a separate E3 ligase pathway to destroy tumor-suppressing proteins, causing heightened cellular proliferation and the transition from normal cell to tumor.. Skp2s E3 ligase activity is required for tumorigenesis, but not involved at all in metastasis, Lin said. Lin and colleagues also previously found that Skp2 blocks cellular senescence - a halt in cell division - in cancer cells.. The research team then found that Skp2 recruits two other proteins, p300 and Miz1, to join Myc and form the complex that transcribes RhoA. Experiments in a mouse model of breast cancer metastasis to the lung showed that deficiency of either Myc, Skp2 or Miz1 restricted metastasis, while overexpression of each of the three proteins ...
Read about how researchers discovered that a densely packed tumor environment triggers cancer spread by switching on metastasis genes.
Free Online Library: New candidate drug stops cancer metastasis and regenerates nerve cells. by Asian News International; News, opinion and commentary General interest Cancer Care and treatment Drug therapy Cancer metastasis Cancer treatment G proteins Metastasis Neurons
Many cancer cell types, as well as their metastases, express high levels of CD44. Whereas some tumors, such as gliomas, exclusively display CD44s, other neoplasms, including brain metastases, gastrointestinal cancer, pancreatic adenocarcinoma, bladder cancer, uterine cervical cancer, breast cancer and non-Hodgkins lymphomas, additionally and sometimes preferentially express CD44 variants. Hence, CD44, particularly its variants, may be used as diagnostic or prognostic markers of at least some human malignant diseases. Furthermore, it has been demonstrated in animal models that upon transfection with CD44s, or CD44v cDNA, nonmetastatic tumor cells acquire metastatic potential. In addition, injection of reagents interfering with CD44-ligand interaction (e.g. CD44s- or CD44v-specific mAb) inhibit local tumor growth and metastatic spread in murine species. In this context, CD44 may confer a growth advantage on some neoplastic cells, and consequently could be used as a target for cancer therapy. The ...
A chip developed by mechanical engineers at Worcester Polytechnic Institute (WPI) can trap and identify metastatic cancer cells in a small amount of blood drawn from a cancer patient. The breakthrough technology uses a simple ...
Côté and his team have recently demonstrated that there is a protein - AXL, that influences metastasis in HER2-positive cancer. Cells that have high levels of AXL have more chances to detach from the tumor and cause metastases.. The study was conducted on mice with samples of tumor cells from patients with cancer. But even with no study on mice, statistics show that women with less AXL present have a better chance of survival.. Based on this discovery, a treatment targeting AXL could reduce the risk of metastasis, explains Côté.. There is a drug therapy that inhibits AXL, and the IRCM researchers have administered it to mice used in their study. They discovered that metastases were less likely to develop. At the moment, the drug is tested in different therapies, and if future tests are successful, this drug could treat patients with breast cancer, complementing the treatments that focus on the tumor.. Côté added that he and his team are still working in the lab:. At the moment, we are ...
Cancer is a heterogeneous disease of rapidly dividing cells with multiple mechanisms of survival. In one such survival mechanism, cancerous cells metastasize to a location distal from the original tumor. The complex process of metastasis often requires a cell to undergo multiple transformative events. First, a cancerous cell must break down the extracellular matrix and break contacts with adjacent cells to migrate from the original tumor through a blood or lymphatic vessel wall. The cancerous cell then circulates through the bloodstream, adheres to the vessel wall at a distal location, and migrates through the blood vessel again. Ultimately, the metastatic cell establishes a new site for growth, forming a secondary tumor. Tumor metastases are typically found first in the lymph nodes near the primary tumor, and only later at other distal locations. Metastatic tumors often prove difficult to treat because they may continually metastasize to multiple locations. New metastatic mechanisms are ...
Cancer is a heterogeneous disease of rapidly dividing cells with multiple mechanisms of survival. In one such survival mechanism, cancerous cells metastasize to a location distal from the original tumor. The complex process of metastasis often requires a cell to undergo multiple transformative events. First, a cancerous cell must break down the extracellular matrix and break contacts with adjacent cells to migrate from the original tumor through a blood or lymphatic vessel wall. The cancerous cell then circulates through the bloodstream, adheres to the vessel wall at a distal location, and migrates through the blood vessel again. Ultimately, the metastatic cell establishes a new site for growth, forming a secondary tumor. Tumor metastases are typically found first in the lymph nodes near the primary tumor, and only later at other distal locations. Metastatic tumors often prove difficult to treat because they may continually metastasize to multiple locations. New metastatic mechanisms are ...
This increased metastatic cell line was derived using an in vivo selection process of highly metastatic cells from a population of poorly metastatic tumor cells, A375  (ATCC CRL-1619). The A375-M1 (ATCC CRL-3222) cell line was derived by i.v. injection of A375 cells into nude mice. Lung metastases were harvested and amplified in vitro as cell lines. The A375-M1 cell line was reinjected into mice for a second round of selection, lung metastases harvested and amplified in vitro as A375-M2 (ATCC CRL-3223) cells. The A375-M1 and A375-M2 cell lines were  transfected with a plasmid containing the ecotropic receptor for murine retrovirus and selected for neomycin resistance. This is useful for RNAse protection assays.
Bone metastases from breast cancer are common, causing significant morbidity. Preclinical data of dasatinib, an oral small molecule inhibitor of multiple oncogenic tyrosine kinases, suggested...
Metastasis causes the death of patients with solid cancers. The core molecular mechanism of metastasis remains largely unknown. The research of Dr. Zhang John Weihuas laboratory focuses on understanding the following metastasis-related molecular mechanisms:. 1. The tyrosine kinase independent function of the epidermal growth factor receptor, EGFR.. 2. The impact of organ microenvironment on the energy metabolism of cancer metastasis.. 3. The role of intracellular ATP levels of cancer cells in the development of cancer metastasis.. ...
Metastases, or secondary tumours, cause around 90 per cent of all deaths from cancer. The ability to gain knowledge as soon as possible about the cancer cells tendency to spread and form metastases could save many lives.. The Cellrace research is based on studies of a biopsy on a specially designed nanosurface.. It is not possible to study the cells movements and behaviour on a microscope slide, as that is not their natural environment. On our nanosurface, we have imitated critical properties from the environment in which they usually operate, i.e. in the body. There we can study them in real time, says Michael Andäng.. At present there is a prototype and the researchers have been able to show statistically significant differences between metastasising cells and non-metastasising cells.. Now we are refining the product and preparing to collaborate with clinics. For example, we want to repeat the tests with recently obtained biopsies. ...
The second major focus of our research is the spread of cancer from its initial site of growth to other locations in the body (metastasis), which is a major factor influencing the likelihood of successful treatment. The formation of metastasis by tumour cells is thought to be dependent on the expression of specific phenotypes by individual tumour cells. Our research is examining metastatic phenotypes that are expressed only transiently and that may be induced by exposure of tumour cells to conditions, such as hypoxia, which occur in the tumour microenvironment. Recent clinical results have suggested that tumours that contain substantial hypoxic regions may be more likely to form metastases. We have found in animal model systems that exposure to hypoxia, both in vitro and in vivo, can cause transient increases in the metastatic potential of tumour cells and that exposure to transient hypoxic episodes may be particularly important for this increased metastatic potential. We are examining the ...
Colon cancer is one of the most frequent malignant diseases worldwide. About 50% of the patients develop distant metastasis. These patients have only few therapy options and very poor survival rates. Therefore cancer research focuses on the identification of novel molecular markers to provide a better prognosis of the metastatic risk. Identified high-risk patients would get access to an early, individualized therapy. MACC1 (metastasis associated in colon cancer 1) is a newly identified gene that is overexpressed in colon carcinomas and their distant metastases. The MACC1 domain structure is characteristic for proteins of the receptor tyrosine kinase signalling pathways. Aim of this study was the analysis of the cellular function of MACC1, its role in tumor progression and its evaluation as a molecular, prognostic marker for metastasis. MACC1 overexpressing tumor cells revealed higher migratory, invasive, and proliferative potential in in vitro assays. The impact of MACC1 on the metastatic ...
Endpoints:. - Response Rate, Disease control rate, The duration of overall response, Overall survival, PFS, Time to treatment failure, Quality of Life, Incidence of AEs, Frequency and nature of serious adverse reactions (SADRs), Premature withdrawals. Statistical methods:. Assuming a randomization ratio of 1:1, 282 deaths are required in order to achieve a power of 80% of detecting a hazard ratio of 0.72 in favour of one of the two sequences, translating in an increase of median survival time from 10 to 14 months, with a type I error of 5%, two-sided, using the Mantel-Cox version of the log-rank test. With a uniform accrual period of 3 years and a follow-up of 18 months, about 350 patients will be needed to reach the target number of events.. All statistical analyses will be based on an intention-to-treat approach. CONSORT rules will be applied to describe study flow and protocol deviations.. All OS and PFS curves will be drawn with the Kaplan-Meier method. Results will be presented as Hazard ...
Oligometastatic prostate cancer has been considered an intermediate state between localized disease and widespread metastases, but there is no
The most widely used staging system for colorectal cancer is the AJCC tumor, nodes, metastasis (TNM) classification system, which classifies patients into prognostic groups according to the depth of the primary tumor, presence of regional LN metastases, and evidence of distant metastases. Recently, the AJCC TNM stage was updated and the T and N stages were further specified to improve prognostic capacity. More emphasis has been made to the number of retrieved malignant LNs. Accordingly, pN1 (metastasis in 1 to 3 regional LNs) has been subdivided into pN1a (metastasis in 1 regional LN) and pN1b (metastasis in 2 to 3 regional LNs), and pN2 (metastasis in 4 or more regional LNs) has been subdivided into pN2a (metastasis in 4 to 6 regional LNs) and pN2b (metastasis in 7 or more regional LNs).11. However, the number of malignant LNs in rectal cancer depends on the number of retrieved LNs, which varies with treatment, patient, and tumor characteristics. There is, in practice, wide variation in the ...
BARCELONA - It is clinically feasible to measure breast tumor cells in a patients circulation, according to the findings of an observational study.. The next step is to determine whether the presence of these cells is truly predictive of impending recurrence or metastasis.. Breast cancer kills only if it metastasizes, so it is important to identify the earliest signs of metastasis. Measuring circulating tumor cells (CTCs) may be a key step in this direction, said Dr. Julia Jueckstock of the department of obstetrics and gynecology, Ludwig-Maximilians University, Munich, where the technique is being pioneered.. Earlier findings showing that CTCs can be measured in bone marrow samples suggest that the presence of tumor cells outside the primary tumor site are indeed predictive of metastasis and poor prognosis. But the difficulty of obtaining bone marrow makes this approach impractical for routine clinical use. Analysis of peripheral blood is potentially much more useful.. Dr. Jueckstock and her ...
SCC-S2/GG2-1/NDED (approved gene symbol TNFAIP8) is a transcription factor NF-kappaB-inducible, antiapoptotic, and oncogenic molecule. In this study, we examined the role of SCC-S2 in invasion and experimental metastasis. We demonstrate that expression of SCC-S2 cDNA in MDA-MB 435 human breast cance …
Find helpful learner reviews, feedback, and ratings for Understanding Cancer Metastasis from 존스홉킨스대학교. Read stories and highlights from Coursera learners who completed Understanding Cancer Metastasis and wanted to share their experience. A big thanks to John Hopkins University for this course the faculty of this university is one of the...
PRIMARY OBJECTIVES:. I. To determine whether every-12-week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma involving bone, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization.. SECONDARY OBJECTIVES:. I. To compare pain scores (Brief Pain Inventory) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing.. II. To compare the functional status (Eastern Cooperative Oncology Group [ECOG] performance status) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing.. III. To compare the incidence of osteonecrosis of the jaw in patients with metastatic breast cancer, ...
TY - JOUR. T1 - Enhanced Metastatic Recurrence Via Lymphatic Trafficking of a High-Metastatic Variant of Human Triple-Negative Breast Cancer After Surgical Resection in Orthotopic Nude Mouse Models. AU - Yano, Shuuya. AU - Takehara, Kiyoto. AU - Tazawa, Hiroshi. AU - Kishimoto, Hiroyuki. AU - Kagawa, Shunsuke. AU - Bouvet, Michael. AU - Fujiwara, Toshiyoshi. AU - Hoffman, Robert M.. PY - 2017/3/1. Y1 - 2017/3/1. N2 - We previously developed and characterized a highly invasive and metastatic triple-negative breast cancer (TNBC) variant by serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. Eventually, a highly invasive and metastatic variant of human TNBC was isolated after lymph node metastases was harvested and orthotopically re-implanted into the mammary gland of nude mice for two cycles. The variant thereby isolated is highly invasive in the mammary gland and metastasized to lymph nodes in 10 of 12 mice compared to 2 of 12 of the parental cell line. In the ...
Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumours, secondaries or stage 4 breast cancer, is a stage of breast cancer where the disease has spread to distant sites beyond the axillary lymph nodes. There is no cure for metastatic breast cancer. There is no stage after IV. It usually occurs several years after the primary breast cancer, although it is sometimes diagnosed at the same time as the primary breast cancer or, rarely, before the primary breast cancer has been diagnosed. Metastatic breast cancer cells frequently differ from the preceding primary breast cancer in properties such as receptor status. The cells have often developed resistance to several lines of previous treatment and have acquired special properties that permit them to metastasize to distant sites. Metastatic breast cancer can be treated, sometimes for many years, but it cannot be cured. Distant metastases are the cause of about 90% of deaths due to breast cancer. Breast ...
Purpose Reports have suggested that metastatic site is an important predictor of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC), but these were based on a limited number of patients. We investigate the impact of site of metastases on OS of a substantial sample of men with mCRPC who received docetaxel chemotherapy in nine phase III trials. Patients and Methods Individual patient data from 8,820 men with mCRPC enrolled onto nine phase III trials were combined. Site of metastases was categorized as lymph node (LN) only, bone with or without LN (with no visceral metastases), any lung metastases (but no liver), and any liver metastases. Results Most patients had bone with or without LN metastases (72.8%), followed by visceral disease (20.8%) and LN-only disease (6.4%). Men with liver metastases had the worst median OS (13.5 months). Although men with lung metastases had better median OS (19.4 months) compared with menwith liver metastases, they had ...
In this article, we report the derivation of highly metastatic human melanoma cell lines from poorly metastatic parental lines using an animal metastasis model. We subsequently identified a metastasis aggressiveness gene signature by comparing the gene expression patterns of tumor samples from the highly metastatic derivatives with those from their parental lines. By comparisons with gene expression data from human clinical samples, we found that expression of this metastasis gene signature in human melanoma metastases correlates with poor survival of the corresponding patients. The signature is able to segregate melanoma-bearing patients into three groups, one of which has a significantly lower survival probability. This suggests that the signature provides an indication of aggressiveness of the melanoma metastases rather than of metastasis per se, similar to the lung metastasis signature reported by Minn et al. (10). This result has been confirmed by alternative methods such as GSEA and ...
Apart from the breast tumor cells, the resident stromal cells also contribute to tumor survival. Links to carefully selected news and features about metastatic breast cancer research. Metastatic breast cancer occurs when the cancer spreads from the breast to another part of the body. Taking breaks in treatment when the disease is under control and you are feeling good can make a big difference in your quality of life. [23] In women with metastatic breast cancer who do not have triple negative disease, there is little or no survival benefit and excess toxicity from platinum-based regimens. You dont have to go through metastatic breast cancer alone. Integrin-mediated tumor cell adhesion to ECM proteins can trigger signal transduction and cause upregulation of gene expression, increased tyrosine phosphorylytion of the focal adhesion kinase, and activation and nuclear translocation of mitogen-activated protein (MAP) kinases. Sometimes when people are diagnosed with metastatic cancer, doctors Its
Metastasis is a major clinical challenge for cancer treatment. Emerging evidence suggests that aberrant epigenetic modifications contribute significantly to tumor formation and progression. However, the drivers and roles of such epigenetic changes in tumor metastasis are still poorly understood. Using bioinformatic analysis of human breast cancer gene-expression data sets, we identified histone demethylase RBP2 as a putative mediator of metastatic progression. By using both human breast cancer cells and genetically engineered mice, we demonstrated that RBP2 is critical for breast cancer metastasis to the lung in multiple in vivo models. Mechanistically, RBP2 promotes metastasis as a pleiotropic positive regulator of many metastasis genes, including TNC. In addition, RBP2 loss suppresses tumor formation in MMTV-neu transgenic mice. These results suggest that therapeutic targeting of RBP2 is a potential strategy for inhibition of tumor progression and metastasis. ...
Accumulated evidence shows that many cancers including prostate cancer disseminate to metastatic sites early in the natural history of disease and can remain undetected and quiescent for extended periods of time.3, 4, 10 In one recent report, disseminated prostate cancer cells (DTCs) can be detected in the bone marrow of 57% men who are without evidence of disease after prostatectomy. With a median follow-up of 42 months, 52% of those with DTCs have not recurred, including patients who still have DTCs 12 years after surgery.5 Thus, in the context of prostate cancer recurrence, metastatic colonization, or the progressive outgrowth of disseminated cancer cells within a secondary site into clinically manifested metastases, is a particularly critical aspect to the multistep metastatic process.7, 35 The molecular factors that control the survival and eventual growth of these disseminated cells are largely unknown.. Experimental modulation of metastasis suppressor genes preclinically affords the ...
TY - JOUR. T1 - Suppression of early hematogenous dissemination of human breast cancer cells to bone marrow by retinoic acid-induced 2. AU - Werner, Stefan. AU - Brors, Benedikt. AU - Eick, Julia. AU - Marques, Elsa. AU - Pogenberg, Vivian. AU - Parret, Annabel. AU - Kemming, Dirk. AU - Wood, Antony W.. AU - Edgren, Henrik. AU - Neubauer, Hans. AU - Streichert, Thomas. AU - Riethdorf, Sabine. AU - Bedi, Upasana. AU - Baccelli, Irene. AU - Jucker, Manfred. AU - Eils, Roland. AU - Fehm, Tanja. AU - Trumpp, Andreas. AU - Johnsen, Steven. AU - Klefstrom, Juha. AU - Wilmanns, Matthias. AU - Muller, Volkmar. AU - Pantel, Klaus. AU - Wikman, Harriet. PY - 2015/5/1. Y1 - 2015/5/1. N2 - Regulatory pathways that drive early hematogenous dissemination of tumor cells are insufficiently defined. Here, we used the presence of disseminated tumor cells (DTC) in the bone marrow to define patients with early disseminated breast cancer and identified low retinoic acid-induced 2 (RAI2) expression to be ...
Dissemination of breast cancers to the brain is associated with poor patient outcome and limited therapeutic options. In this study we sought to identify novel regulators of brain metastasis by profiling mouse mammary carcinoma cells spontaneously metastasising from the primary tumour in an immunocompetent syngeneic host. 4T1 mouse mammary carcinoma sublines derived from primary tumours and spontaneous brain and lung metastases in BALB/c mice were subject to genome-wide expression profiling. Two differentially expressed genes, Id2 and Aldh3a1, were validated in in-vivo models using mouse and human cancer cell lines. Clinical relevance was investigated in datasets of breast cancer patients with regards to distant metastasis-free survival and brain metastasis relapse-free survival. The role of bone morphogenetic protein (BMP)7 in regulating Id2 expression and promoting cell survival was investigated in two-dimensional and three-dimensional in-vitro assays. In the spontaneous metastasis model, expression
To understand colon cancer metastasis, we earlier analyzed a mouse model that developed liver metastasis of cancer cells disseminated from the spleen. We suggested that CCR1(+) bone marrow (BM)-derived cells are recruited to the microenvironment of disseminated colon cancer cells, and produce metall …
A systematic comparison of metastatic breast cancer cells to healthy breast cells revealed dramatic differences between the two cell lines in their mechanics, migration, oxygen response, protein production, and ability to stick to surfaces.. The new study details how cells make the transition from nonmalignant to metastatic, a process that is not well understood.. By bringing together different types of experimental expertise to systematically compare metastatic and nonmetastatic cells, we have advanced our knowledge of how metastasis occurs, says Robert Austin, professor of physics at Princeton University.. The study also found that metastatic cells recover more rapidly from the stress of a low-oxygen environment than nonmetastatic cells, which is consistent with previous studies. Although the low-oxygen environment did kill many of the metastatic cells, the survivors rebounded vigorously, underscoring the likely role of individual cells in the spread of ...
Breast cancer metastatic mouse models are experimental approaches in which mice are genetically manipulated to develop a mammary tumor leading to distant focal lesions of mammary epithelium . Recent ameliorations in maneuvering the mouse genome have provided the technology to induce mammary cancers in mice arising from genetic mutations that have been identified in human cancer. This means models can be generated based upon molecular lesions consistent with the human disease. Metastasis is a process of migration of tumour cells from the primary cancer site to a distant location where the cancer cells form secondary tumors. Metastatic breast cancer represents the most devastating attribute of cancer and it is considered an advanced-stage event. Human breast cancer metastasizes to multiple distant organs such as the brain, lungs, bones and liver. The classical theory developed in the early 70s anticipated that metastasis is due to genetically determined subpopulations in primary tumours. The ...
Due to the effi cient screening and early detection most breast cancer cases are recognized today in early stage. Approximately 5% of newly detected cases have distant metastasis. In Hungary the situation is worse. Early stage disease will relapse in about 30%, mainly with distant metastasis. Metastatic breast cancer is incurable disease, except some rare, special cases. As systemic therapeutic options are developing rapidly, most breast cancer subtypes can be treated successfully and long term survival is not rare. Primary objective of the treatment is increasing overall survival and quality of life, by decreasing disease related symptoms. In this review we summarize the systemic therapeutic options of metastatic breast cancer according to the subtypes. It is recommended to use an individual treatment plan for every patient.. ...
Most ovarian cancer patients present with disseminated disease at the time of their diagnosis, which is one of the main reasons for their poor prognosis. Metastasis is a multi-step process and a clear understanding of the mechanism of regulation of these steps remains elusive. Productive reciprocal interactions between the metastasizing ovarian cancer cells and the microenvironment of the metastatic site or the tumor microenvironment play an important role in the successful establishment of metastasis. Much progress has been made in the recent past in our understanding of such interactions and the role of the cellular and acellular components of the microenvironment in establishing the metastatic tumors. This review will outline the role of the microenvironmental components of the ovarian cancer metastatic niche and their role in helping establish the metastatic tumors. Special emphasis will be given to the mesothelial cells, which are the first cells encountered by the cancer cells at the site of
Jill Cohen, on living with stage IV breast cancer for 13 years. Learn more about metastatic breast cancer and support the Beyond the Breast Campaign.In August I celebrated 13 years of living with metastatic breast cancer. Yes, I celebrated - wouldnt you? I called it my
Metastasis is the major cause of treatment failure in cancer patients and of cancer-related deaths. This editorial discusses how cancer metastasis may be better perceived and controlled. Based on big-data analyses, a collection of 150 important pro-metastatic genes was studied. Using The Cancer Genome Atlas datasets to re-analyze the effect of some previously reported metastatic genes-e.g., JAM2, PPARGC1A, SIK2, and TRAF6-on overall survival of patients with renal and liver cancers, we found that these genes are actually protective factors for patients with cancer. The role of epithelial-mesenchymal transition (EMT) in single-cell metastasis has been well-documented. However, in metastasis caused by cancer cell clusters, EMT may not be necessary. A novel role of epithelial marker E-cadherin, as a sensitizer for chemoresistant prostate cancer cells by inhibiting Notch signaling, has been found. This editorial also discusses the obstacles for developing anti-metastatic drugs, including the lack of high
Establishment of skeletal metastasis involves bidirectional interactions between the tumor cell and the cellular elements in the bone microenvironment. A better understanding of the pathophysiology of bone metastasis will be critical in developing the means to prevent bone metastasis or inhibit its progression. The receptor activator of nuclear factor-κB (RANK)/RANK ligand pathway has emerged as the key pathway regulating osteolysis in skeletal metastasis. A number of candidate factors, including the Wnt (wingless int) proteins, endothelin-1, and bone morphogenetic proteins, have been implicated in the establishment of osteoblastic metastasis. The complex nature of tumor-bone microenvironment interactions and the presence of multiple pathways that lead to bone metastasis suggests that simultaneous targeting of these pathways in the metastatic cascade are required for effective treatment. This review discusses current understanding of the pathophysiologic mechanisms that underlie the establishment of
Sunitinib is a potent and clinically approved tyrosine kinase inhibitor that can suppress tumour growth by inhibiting angiogenesis. However, conflicting data exist regarding the effects of this drug on the growth of metastases in preclinical models. Here we use 4T1 and RENCA tumour cells, which both form lung metastases in Balb/c mice, to re-address the effects of sunitinib on the progression of metastatic disease in mice. We show that treatment of mice with sunitinib prior to intravenous injection of tumour cells can promote the seeding and growth of 4T1 lung metastases, but not RENCA lung metastases, showing that this effect is cell line dependent. However, increased metastasis occurred only upon administration of a very high sunitinib dose, but not when lower, clinically relevant doses were used. Mechanistically, high dose sunitinib led to a pericyte depletion effect in the lung vasculature that correlated with increased seeding of metastasis. By administering sunitinib to mice after intravenous
TY - JOUR. T1 - Anti-human CD73 monoclonal antibody inhibits metastasis formation in human breast cancer by inducing clustering and internalization of CD73 expressed on the surface of cancer cells. AU - Terp, Mikkel G. AU - Olesen, Kristina A. AU - Christensen, Eva Arnspang. AU - Lund, Rikke R. AU - Lagerholm, B Christoffer. AU - Ditzel, Henrik J. AU - Leth-Larsen, Rikke. PY - 2013. Y1 - 2013. N2 - Recent studies have shown that Abs that target the cell-surface enzyme CD73 (ecto-5-nucleotidase) reduce growth of primary tumors and metastasis in syngenic mice by inhibiting the catalytic activity of CD73, and thus increasing the activity of cytotoxic T lymphocytes. In this article, we report another anticancer mechanism of anti-CD73 Abs and show that an anti-CD73 mAb (AD2) inhibits metastasis formation by a mechanism independent of CD73 catalytic activity and inhibition of primary tumor growth. This mechanism involves clustering and internalization of CD73, but does not require cross-linking of ...
Cancer cells can break away from where they first formed and travel through the blood or lymph system to form new tumors (metastases) in other parts of the body. Metastases of the lung are tumors in the lung that originated from a primary tumor located in a different part of the body.. Metastatic cancer has the same name as the primary cancer. For example, breast cancer that spreads to the lung is called metastatic breast cancer, not lung cancer. It is treated as a stage IV breast cancer rather than a primary lung cancer. Limited metastases to the lung can be treated with resection or ablation.. ...
On September 28, 2017, the FDA approved abemaciclib (Verzenio; Eli Lilly), a cyclin-dependent kinase (CDK)4/CDK6 inhibitor, in combination with fulvestrant, for the treatment of women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer that progressed after endocrine therapy, and as monotherapy for HR-positive, HER2--negative advanced or metastatic breast cancer that progressed after endocrine therapy and previous chemotherapy in the metastatic setting.
Data presented above show that the human fibrosarcoma cell line HT1080 is able to inhibit the growth of experimental metastases. These results suggest that this inhibition is due to the antiangiogenic activity of circulating TSP-1 that is released by the tumor cells in vivo, circulates at effective levels, and makes the tumor-bearing animals unable to mount an angiogenic response. The data also demonstrate the in vivo efficacy of soluble TSP-1, showing it can be used as a drug to prevent the growth of experimental metastases.. HT1080 produced concomitant tumor resistance directly by secreting active TSP-1, unlike previously studied rodent tumors that create an antiangiogenic state when the tumor cells, or associated stromal elements (29), secrete enzymes or activators of enzymes (30) that generate inhibitors from other molecules. We saw no significant evidence for in vivo breakdown of tumor-derived TSP-1 to fragments smaller than the 140 kDa monomer, a molecule that is as effective an ...
TY - JOUR. T1 - Correction. T2 - De-acetylation and degradation of HSPA5 is critical for E1A metastasis suppression in breast cancer cells [Oncotarget. 5, 21, (2014) (10558-70)] doi: 10.18632/oncotarget.2510.. AU - Chang, Yi Wen. AU - Chen, Hsin An. AU - Tseng, Chi Feng. AU - Hong, Chih Chen. AU - Ma, Jui Ti. AU - Hung, Mien Chie. AU - Wu, Chih Hsiung. AU - Huang, Ming Te. AU - Su, Jen Liang. PY - 2016. Y1 - 2016. N2 - Present: Due to an error made during the assembly of Figure 1A. The data of migration and invasion ability of HS578T groups and HBL100 groups are exist in the same excel file and we misplaced the histogram of HS578T groups as the HBL100 groups histogram, caused the inadvertently duplication during the preparation and assembly of Figure 1A. We apologize for our careless mislabelling and this error has been corrected now. The experimental results and conclusions of this article are not affected by this modification. We deeply regret this error and apologize to the scientific ...
Despite decades of effort, little progress has been made to improve the diagnosis and treatment of cancer metastases. In particular, because of the heterogeneity of cancer and its ability to develop resistance to current treatments that target biochemical markers, new targeting strategies are urgently needed. Inspired by the tight correlation between increases in tissue stiffness and breast cancer metastatic niches found in recent studies (13, 15, 17, 18, 45) and the fact that MSCs differentiate to specific lineages depending on the stiffness of the microenvironment (28), we have developed a class of cancer therapeutics that directly target the mechanoenvironmental cues of cancer metastases. The MRCS is an attempt to directly interrogate the mechano-niche in vivo and apply it for localized delivery of agents including imaging reporters and therapeutics.. Mechano-niches play vital roles in development, homeostasis, and disease progression, including many types of cancer, and therefore serve as an ...
TY - JOUR. T1 - Computational modeling of pancreatic cancer reveals kinetics of metastasis suggesting optimum treatment strategies. AU - Haeno, Hiroshi. AU - Gonen, Mithat. AU - Davis, Meghan B.. AU - Herman, Joseph M.. AU - Iacobuzio-Donahue, Christine A.. AU - Michor, Franziska. PY - 2012/1/20. Y1 - 2012/1/20. N2 - Pancreatic cancer is a leading cause of cancer-related death, largely due to metastatic dissemination. We investigated pancreatic cancer progression by utilizing a mathematical framework of metastasis formation together with comprehensive data of 228 patients, 101 of whom had autopsies. We found that pancreatic cancer growth is initially exponential. After estimating the rates of pancreatic cancer growth and dissemination, we determined that patients likely harbor metastases at diagnosis and predicted the number and size distribution of metastases as well as patient survival. These findings were validated in an independent database. Finally, we analyzed the effects of different ...
The term metastatic breast cancer means that cancer has spread to organs outside the breast or surrounding lymph nodes, such as the liver, lung, and brain. Metastatic breast cancer is not a curable condition. However, treatment can prolong life, dela
Keywords: LncRNA, FOXF1-AS1, EMT, metastasis, lung cancers Launch As one of the most common causes of cancers related loss of life of the global globe, lung cancers provides become a serious open public wellness issue [1]. Two primary subtypes of lung cancers are called as non-small cell lung cancers (NSCLC) and little cell lung cancers, which accounts for around 80-85% and 15-20% respectively [2]. Although developments in the molecular carcinogenesis and brand-new targeted therapies for NSCLC created significantly in the previous few years [3C5], the general success of sufferers with this disease continues to be low [6 still, 7]. The high fatality is related to early metastasis [8] most likely; nevertheless, the mechanism underlying metastasis is unknown however still. Metastasis of NSCLC is certainly a complicated procedure and modulated by many guidelines [9]. NSCLC cells get away from the principal tumor to a brand-new tissues or body organ when metastasis starts. The primary vital ...
MicroRNA-7 (miR-7) has been observed as a potent tumour suppressor in multiple cancer types including breast cancer. The aim of this study was to investigate th...
Living with metastatic breast cancer can be stressful. Here is a collection of resources and support for individuals living with metastatic breast cancer.
Objectives: Breast cancer has been the second most prevalent and fatal malignancy due to its frequent metastasis to other organs. We aim to study the effects of a key miRNA-mRNA signaling in breast cancer.Results: CNN1 was identified as the key gene in breast cancer by the bioinformatics analysis, and the downregulation of CNN1 in breast cancer tissues and cell lines was observed. Upregulating CNN1 inhibited cell survival, migration, invasion, and adhesion, but enhanced cell apoptosis. miR-106b-5p not only bound to CNN1 mRNA 3’UTR, but also promoted lung metastasis in vivo. Besides, the miR-106b-5p mimic enhanced breast cancer canceration by targeting CNN1 and activating Rho/ROCK1 signaling pathway.Conclusion: Overall, our results proved that miR-106b-5p promoted the metastasis of breast cancer by suppressing CNN1 and activating Rho/ROCK1 pathway.Methods: Bioinformatics analysis was performed to select the key gene in breast cancer. The overexpression and knockdown of Calponin 1 (CNN1) in
Tumor cell migration is a key step in the formation of cancer metastasis. The mammalian target of rapamycin (mTOR), a highly conserved and ubiquitously expressed serinethreonine kinase, has been intensely studied for over a decade as a central regulator of cell growth, proliferation, differentiation, and survival. Recent data have shown that mTOR also plays a critical role in the regulation of tumor cell motility and cancer metastasis. Here, we briefly review recent advances regarding mTOR signaling in tumor cell motility. We also discuss recent findings about the mechanism by which rapamycin, a specific inhibitor of mTOR, inhibits cell motility in vitro and metastasis in vivo.. ...
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Bone metastasis is a common event in advanced cancers such as prostate, breast, lung, and renal cancers. Radiation therapy has been widely used for bone metastasis. However, it remains a challenging therapy because no radiation therapeutic guidelines, including radiation dose, radiation field, and fractionation, for patients with bone metastasis have been established. Many randomized controlled trials for bone metastasis have been carried out. They showed no significant difference in pain relief with a short course of radiation therapy such as 8 Gy/1 Fr and 20 Gy/5 Fr or with a long course of radiation therapy such as 30 Gy/10 Fr, 37.5 Gy/15 Fr, and 40 Gy/20 Fr. Toxicity rates with short and long courses were also the same. Recurrence rate at 2 years, however, was significantly higher in patients irradiated with a short course than in patients irradiated with a long course. Those trials also showed that response rate is affected by patients age, performance state, tumor type, pathological state, number
article: A rare case of metastatic deposits of cervical carcinoma in the heart - Gazzetta Medica Italiana - Archivio per le Scienze Mediche 2019 March;178(3):154-6 - Minerva Medica - Riviste
The establishment of distant metastases depends on the capacity of small numbers of cancer cells to regenerate a tumor after entering a target tissue. The mechanisms that confer this capacity remain to be defined. Here we identify a role for the transcriptional inhibitors of differentiation Id1 and Id3 as selective mediators of lung metastatic colonization in the triple negative [TN, i.e., lacking expression of estrogen receptor and progesterone receptor, and lacking Her2 (human epidermal growth factor receptor 2) amplification] subgroup of human breast cancer. Although broad expression of Id1 has recently been documented in tumors of the rare metaplastic subtype, here we report that rare Id1-expressing cells are also present in the more common TN subset of human breast tumors but not in other subtypes. We also provide evidence that Id1 expression is enriched in clinically obtained hormone receptor negative lung metastases. Functional studies demonstrate that Id1 and its closely related family ...
Study of MK-1454 Alone or in Combination With Pembrolizumab (MK-3475) in Participants With Advanced / Metastatic Solid Tumors or Lymphomas (MK-1454-001) - NCT03010176
Of the nine patients in the UCLA study who underwent biopsy, four had tumors identified as high-risk for aggressive metastasis, and five were identified as low-risk. When physicians know upfront which patient has a poor prognosis, they will monitor the person more closely to detect metastasis earlier and consider more aggressive treatments to increase their chance of survival, Young emphasized. Knowledge of metastatic risk will also help patients and their physicians decide whether to pursue clinical trials of experimental therapies that target metastasis.. Patients understand that no good treatment exists after their cancer spreads -- everyone wants to know what their metastasis risk is, she added. If the risk is low, its a giant relief and emotional burden off their shoulders. If the risk is high, it enables them to plan arrangements for their family and finances, and make the most of their remaining time alive. Pioneered by UCLA ophthalmic pathologist Dr. Ben Glasgow, the technique of ...
Results Three new genes from the colorectal cancer (CRC) metastasis signature, BOP1, CKS2 and NFIL3, were identified as direct transcription targets of β-catenin/TCF4. Overexpression and knocking down of these genes in CRC cells promoted and inhibited, respectively, experimental metastasis in mice, EMT and cell motility in culture. Cell migration was repressed by interfering with distinct signalling systems through inhibitors of PI3K, JNK, p38 mitogen-activated protein kinase and/or mTOR. Gene expression profiling identified a series of migration-promoting genes, which were induced by BOP1, CKS2 and NFIL3, and could be repressed by inhibitors that are specific to these pathways. ...
The invasive phenotype of breast tumors, determined by characteristics such as tumor cell motility and membrane perturbations, is clearly linked to cytoskeletal function. For example, recent studies have shown that certain metastasis-specific molecules (e.g., CD44v3,8-10 isoform [Bourguignon et al. 1998b, Bourguignon et al. 1999] and its associated matrix metalloproteinase, MMP-9 [Bourguignon et al., 1998b; Yu and Stamenkovic 1999], as well as Rho kinase [Bourguignon et al. 1999]) are closely associated with the cytoskeleton during tumor cell function. To further examine the regulatory mechanism(s) involved in cytoskeleton-mediated oncogenic signaling leading to tumor cell invasion and migration, we have focused on GEFs (the Dbl or DH family), such as Tiam1, which are known to display oncogenic capability and function as upstream activators of Rho-like GTPases (e.g., Rac1 or Cdc42; Woods et al., 1991; Habets et al. 1994; Michiels et al. 1995; Nobes and Hall 1995; Van Leeuwen et al. 1995). In ...