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Heparan sulfate 3-O-sulfotransferase 2 (HS3ST2), an enzyme mediating 3-O-sulfation of heparan sulfate (HS), is silenced by hypermethylation in breast cancer. As HS has an important co-receptor function for numerous signal transduction pathways, the phenotypical changes due to HS3ST2 reexpression were investigated in vitro using high and low invasive breast cancer cell lines. Compared to controls, highly invasive HS3ST2-expressing MDA-MB-231 cells showed enhanced Matrigel invasiveness, transendothelial migration and motility. Affymetrix screening and confirmatory real-time PCR and Western blotting analysis revealed increased expression of several matrix metalloproteinases, cadherin-11, E-cadherin and CEACAM-1, while protease inhibitor and annexin A10 expression were decreased. Low invasive HS3ST2 -expressing MCF-7 cells became even less invasive, with no change in gelatinolytic MMP activity. HS3ST2 expression increased HS-dependent basal and FGF2-specific signaling through the constitutively ...
By using microarray and an invasion/metastasis lung cell line model, we identified the DnaJ-like heat shock protein 40, HLJ1, and found that the expression of HLJ1 correlates negatively with cancer cell invasion ability . Overexpression of HLJ1 can suppress cancer cell invasion in vitro. We further characterize the putative promoter region and investigate the transcriptional regulations of human HLJ1. A serial deletion of the 1.2 kb at the 5′-flanking region of the human HLJ1 gene was subcloned into a vector containing reporter gene and transfected into human lung adenocarcinoma cell line CL1-0, followed by luciferase activity assay. The results indicated that the region from -232 to +176 could drive the basal transcriptional activity of the HLJ1 gene. Sequence analysis of the HLJ1 gene promoter region showed absence of a TATA box, but identified an inverted CCAAT box and four YY1 transcriptional factor-binding sites, which may be important in the regulation of HLJ1 expression. Co- ...
MT1-MMP drives cancer cell invasion and intravasation. (A and B) HT-1080 or SCC-1 cells were incubated alone with TIMP-1, TIMP-2, a 21-bp MT1-MMP siRNA, or a 21
The results of the current study showed the molecular and functional activation of β-catenin by hypoxia in HCC and showed its contribution to hypoxia-induced metastatic phenotypes. The induction of EMT was one of the proinvasive mechanisms augmented by β-catenin during hypoxia. The coexpression of β-catenin and HIF-1α (a marker of hypoxia) in HCC was found to be correlated with metastases and poor prognosis in two independent cohorts of patients. These results confirm the importance of β-catenin in HCC under hypoxic conditions.. Hypoxia plays a critical role in tumor progression (1). Consistent with our previous report (17), it not only facilitated in vitro cell invasion in HCC but also resulted in peritoneal seeding and pulmonary metastasis in an in vivo HAL model. However, the growth of HCC cells and xenografts were suppressed by hypoxia. Further analysis revealed that this could be attributed to the arrest of cell proliferation rather than the induction of apoptosis (Supplementary Fig. ...
Perineural invasion (PNI) is the neoplastic invasion of nerves. PNI is widely recognized as an important adverse pathological feature of many malignancies, including pancreatic, prostate, and head and neck cancers and is associated with a poor prognosis.
Proteolytic degradation of the extracellular matrix plays a crucial role in both cancer invasion and non-neoplastic tissue remodeling processes. In human cancers the components of matrix degrading protease systems (uPA, uPAR, PAI-1 and MMPs) can be expressed by either the non-neoplastic stromal cell …
The initiation and progression of cancer is closely associated with the tumor microenvironment. The overexpression of oncogenes during tumor growth and progression by stromal stimuli can affect the...
Oct 06, 2016 · Malfunction of Rabs-regulating vesicle trafficking could promote cancer invasion. For example, Rab11 is an important component for membrane proteins recycling and proteins transport from TGN to the plasma membrane. Rab11-mediated α6β4 integrin trafficking has been found to contribute to increase cancer cell invasion in breast cancer.
TY - JOUR. T1 - The mode and dynamics of glioblastoma cell invasion into a decellularized tissue-derived extracellular matrix-based three-dimensional tumor model. AU - Koh, Ilkyoo. AU - Cha, Junghwa. AU - Park, Junseong. AU - Choi, Junjeong. AU - Kang, Seok Gu. AU - Kim, Pilnam. PY - 2018/3/1. Y1 - 2018/3/1. N2 - Glioblastoma multiforme (GBM) is the most common brain tumor with very aggressive and infiltrative. Extracellular matrix (ECM) plays pivotal roles in the infiltrative characteristics of GBM. To understand the invasive characteristic of GBM, it is necessary to study cell-ECM interaction in the physiologically relevant biomimetic model that recapitulates the GBM-specific ECM microenvironment. Here, we propose biomimetic GBM-specific ECM microenvironment for studying mode and dynamics of glioblastoma cell invasion. Using tissue decellularization process, we constructed a patient tissue-derived ECM (pdECM)-based three-dimensional in vitro model. In our model, GBM cells exhibited ...
Peroxisome proliferator-activated receptor β (PPARβ) and NaV1.5 voltage-gated sodium channels have independently been shown to regulate human breast cancer cell invasiveness. The n-3 polyunsaturated docosahexaenoic acid (DHA, 22:6n-3), a natural ligand of PPAR, is effective in increasing survival and chemotherapy efficacy in breast cancer patient with metastasis. DHA reduces breast cancer cell invasiveness and it also inhibits PPARβ expression. We have shown previously that NaV1.5 promotes MDA-MB-231 breast cancer cells invasiveness by potentiating the activity of Na(+)/H(+) exchanger type 1 (NHE-1), the major regulator of H(+) efflux in these cells. We report here that DHA inhibited NaV1.5 current and NHE-1 activity in human breast cancer cells, and in turn reduced NaV1.5-dependent cancer cell invasiveness. For the first time, we show that antagonizing PPARβ, or inhibiting its expression, reduced NaV1.5 mRNA and protein expression and NaV1.5 current, as well as NHE-1 activity and cell ...
Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, is implicated in many cancers; however, it is unclear specifically which EGFR pathways are involved in triggering tumor cell invasiveness. The abundance of the small guanosine triphosphatase Arf6, which regulates processes such as membrane trafficking and endocytosis, correlates with the invasiveness of malignant breast cancer cells. In this context, Morishige et al. used small interfering RNA (siRNA) to individually decrease the expression of the 10 genes that encode guanine nucleotide exchange factors (GEFs) that activate Arf family proteins in the invasive human breast cancer cell line MDA-MB-231. GEP100 was the only ArfGEF whose depletion resulted in the inhibition of MDA-MB-231 invasion activity, as measured by an in-gel invasiveness assay. Coimmunoprecipitation studies showed that EGF treatment of MDA-MB-231 cells triggered the association of GEP100 with EGFR. In transfected Cos-7 cells, the authors showed the ...
Purified Cell Invasion Assay (Basement Membrane), 24-well, 8 μm from Creative Biomart. Cell Invasion Assay (Basement Membrane), 24-well, 8 μm can be used for research.
TY - JOUR. T1 - Tumor volume and lymphovascular space invasion as a prognostic factor in early invasive adenocarcinoma of the cervix. AU - Murakami, Isao. AU - Fujii, Takuma. AU - Kameyama, Kaori. AU - Iwata, Takashi. AU - Saito, Miyuki. AU - Kubushiro, Kaneyuki. AU - Aoki, Daisuke. PY - 2012/6. Y1 - 2012/6. N2 - Objective: The aim of this study was to investigate the risk and recurrence of early invasive adenocarcinoma of the cervix, and to determine whether non-radical methods of management could be performed. Methods: The medical and histopathological records of 50 patients with early invasive adenocarcinoma of the cervix treated at Keio University Hospital between 1993 and 2005 were reviewed, and compared with the literature. Results: The median follow-up period was 64.3 months. The depth of stromal invasion was ≤3 mm in 33 cases and ,3 mm, but ≤5 mm in 17 cases. The horizontal spread was ≤7 mm in 25 cases and ,7 mm in 25 cases. One of the 33 cases that had tumor volumes of ≤500 mm ...
Background Stromal fibroblasts can contribute to tumor invasion through the release of matrix metalloproteinases (MMPs). Population studies have suggested that single nucleotide polymorphisms (SNPs) in MMP genes influence levels of expression and may be associated with breast cancer risk and with disease progression. This study directly examined the impact of MMP SNP genotype on the ability of host fibroblasts to promote tumor cell invasion. Methods Primary breast fibroblasts were isolated from patients with (n = 13) or without (n = 19) breast cancer, and their ability to promote breast cancer cell invasion was measured in in vitro invasion assays. Fibroblast invasion-promoting capacity (IPC) was analyzed in relation to donor type (tumor or non-tumor patient), MMP-1, MMP-3, and MMP-9 SNP genotype and MMP activity using independent samples t test and analysis of variance. All statistical tests were two-sided. Results Tumor-derived fibroblasts promoted higher levels of invasion than normal ...
Platelet-cancer cell interactions play a key role in successful haematogenous metastasis. Disseminated malignancy is the leading cause of death among ovarian cancer patients. It is unknown why different ovarian cancers have different metastatic phenotypes. To investigate if platelet-cancer cell interactions play a role, we characterized the response of ovarian cancer cell lines to platelets both functionally and at a molecular level. Cell lines 59 M and SK-OV-3 were used as in vitro model systems of metastatic ovarian cancer. Platelet cloaking of each cell line was quantified by flow cytometry. Matrigel invasion chamber assays were used to assess the invasive capacity of the cell lines. The induction of an EMT was assessed by morphology analysis and by gene expression analysis of a panel of 11 EMT markers using TaqMan RT-PCR. SK-OV-3 cells adhered to and activated more platelets than 59 M cells (p = 0.0333). Platelets significantly promoted the ability of only SK-OV-3 cells to invade (p ≤ 0.0001).
Sigma-Aldrich offers abstracts and full-text articles by [Hai Zhang, Shanyu Cheng, Min Zhang, Xiuping Ma, Li Zhang, Yipin Wang, Rong Rong, Juan Ma, Shukai Xia, Mingzhan Du, Feng Shi, Jie Wang, Qinyi Yang, Xiaoming Bai, Jing Leng].
4360 Secreted acidic protein rich in cysteine (SPARC) has been suggested as a potential glioma invasion promoting gene. SPARC is highly expressed in human gliomas, promotes glioma invasion, and delays tumor growth in vitro and in vivo. cDNA array reports were performed to determine whether SPARC, which interacts at the cell surface, has an impact on intracellular signaling and downstream gene expression changes that might account for some of its effects on invasion and growth. Additional in vitro studies demonstrated that SPARC delays growth, increases attachment, and modulates migration of tumor cells in extracellular matrix-specific and concentration-dependent manners. It has been reported that SPARC functionally contributes to brain tumor invasion and delays tumor growth in vivo, and that the effects of SPARC are related to the level of SPARC secreted into the extracellular matrix. Thus far, the signaling aspects of glioma migration and invasion are not fully understood. As such, we made an ...
Furin, a subtilisin/kesin-like proprotein convertase (PC), activates membrane-bound MT1-MMP, which facilitates pro-gelatinase A (MMP2). These activated MT1-MMP and MMP2 are involved in cancer cell invasion and metastasis. In this study, we investigate the contribution of MMP2 activated by furin to cellular invasiveness of cumulatively irradiated cells.. Using previously established AMC-HN3 and AMC-HN8 cell line from laryngeal carcinoma patient, we have generated isogenic model of cumulatively irradiated AMC-HN3R and AMC-HN8R cell line, respectively. AMC-HN3R cells were increased furin expression with upregulation of MT1-MMP/MMP2 and their invasiveness by two fold (p , 0.05) compared to AMC-HN3, while AMC-HN8R cells had no differences compared to AMC-HN8. In case of AMC-HN3R, inhibition of furin activity with the synthetic inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethyl-keton, CMK, showed a significant decrease of MT1-MMP/MMP2 and in vitro cellular invasiveness. Tumors obtained after subcutaneous ...
TY - JOUR. T1 - EGFR-mediated carcinoma cell metastasis mediated by integrin αvβ5 depends on activation of c-Src and cleavage of MUC1. AU - Lau, Steven K.M.. AU - Shields, David J.. AU - Murphy, Eric A.. AU - Desgrosellier, Jay S.. AU - Anand, Sudarshan. AU - Huang, Miller. AU - Kato, Shumei. AU - Lim, Ssang Taek. AU - Weis, Sara M.. AU - Stupack, Dwayne G.. AU - Schlaepfer, David D.. AU - Cheresh, David A.. PY - 2012/5/7. Y1 - 2012/5/7. N2 - Receptor tyrosine kinases and integrins play an essential role in tumor cell invasion and metastasis. We previously showed that EGF and other growth factors induce human carcinoma cell invasion and metastasis mediated by integrin αvβ5 that is prevented by Src blockade [1]. MUC1, a transmembrane glycoprotein, is expressed in most epithelial tumors as a heterodimer consisting of an extracellular and a transmembrane subunit. The MUC1 cytoplasmic domain of the transmembrane subunit (MUC1.CD) translocates to the nucleus where it promotes the transcription of ...
Salmonellosis is one of the most common and widely distributed food borne diseases caused by Salmonella enterica serovar Typhi (S.Typhi). Powerful str..
Fig. 3 PTENs intact PDZ binding domain is required for antagonism of PREX2-driven invasion, and the PTEN C2-tail is sufficient to suppress invasion.. (A) PREX2 drives invasion. BT549 cells were transfected as indicated and subjected to invasion assays using an FBS gradient or no gradient. (B) PTEN constructs used in invasion assays. (C) PTEN C2-tail, G129E, and C124S block PREX2-driven invasion. BT549 cells were transfected as indicated, and invasion experiments were performed using an FBS gradient. (D) Immunoblots showing PREX2 and PTEN from cells used in invasion assays. Lysates from breast cancer cell lines with endogenous PTEN are shown. (E) C2-tail antagonizes PREX2-driven invasion in SUM149 cells. SUM149 cells were transfected as indicated, and invasion experiments were performed. (F) Coimmunoprecipitation of PTEN constructs and PREX2. BT549 cells were transfected with V5-PREX2 along with the indicated FLAG-PTEN constructs. (G) Schematic showing the binding of the PTEN PDZ binding domain ...
Die Universität zu Köln ist eine Exzellenzuniversität mit dem klassischen Fächerspektrum einer Volluniversität. Als eine der größen Hochschulen Europas arbeitet sie in Forschung und Lehre auch international auf höchstem Niveau.
Chemotherapy is widely used to treat metastatic disease. However, while many patients initially respond, a high percentage of them ultimately relapse. Cells plated in a monolayer respond much better to cytotoxic therapy than the same cells grown in 3D spheroids, or in xenograft tumors in mice, suggesting that the ECM and stromal cells that make up the tumor microenvironment drive drug resistance. While there has been work highlighting mechanisms of resistance derived from the release of cytokines from stromal cells, the role of the ECM in this process remains understudied in 3D in vitro systems or in vivo using mouse models. In addition, how chemotherapy treatment alters the ECM remains unknown. Finally, most studies focus on the effect chemotherapeutics on cell death, while the potentially dangerous effects of these drugs on tumor cell invasion and metastatic capability remain understudied. Our preliminary data show that chemotherapeutics can have different effects on growth and motility in ...
Celldance 2015: Spying on Cancer Cell Invasion, by Edison Leung with Allison Harney, John Condeelis lab, Albert Einstein College of Medicine.
Perineural invasion (PNI) is thought to be one of the factors responsible for the high rate of tumor recurrence after surgery and the pain generation associated with pancreatic cancer. Signaling via the nerve growth factor (NGF) pathway between pancreatic cancer cells and the surrounding nerves has been implicated in PNI, and increased levels of these proteins have been correlated to poor prognosis. In this study, we examine the molecular mechanism of the NGF signaling pathway in PNI in pancreatic cancer. We show that knocking down NGF or its receptors, TRKA and p75NTR, or treatment with GW441756, a TRKA kinase inhibitor, reduces the proliferation and migration of pancreatic cancer cells in vitro ...
Publications (* co-first): Kim HD*, Sileika TS*, Maniak P, Messersmith PB. Antibacterial performance of polydopamine modified polymer surfaces containing passive and active components. Submitted. 2011 Kim HD, Peyton SR. Bio-inspired materials for parsing matrix physicochemical control of cell migration. Integr Biol. Accepted. 2011 Kim HD*, Hause RJ*, Leung K*, Jones RA. Targeted protein-omic methods are bridging the gap between proteomic and hypothesis-driven protein analysis approaches. Expert Rev Proteomics. Accepted. 2011 Kim HD, Meyer AS, Wagner JP, Alford SK, Wells A, Gertler FB, Lauffenburger DA. Signaling network state predicts Twist-mediated effects on breast cell migration across diverse growth factor contexts. Mol Cell Proteomics. Accepted. 2011 Philippar U, Roussos ET, Oser M, Yamaguchi H, Kim HD, Giampieri S, Wang Y, Goswami S, Wyckoff JB, Lauffenburger DA, Sahai E, Condeelis JS, Gertler FB. A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis. Dev ...
Cell migration & Invasion Assays are important investigate for different cell types and disease states. Read more in this Article.
Isoorientin induces apoptosis, decreases invasiveness, and downregulates VEGF secretion by activating AMPK signaling in pancreatic cancer cells [Corrigendum] Isoorientin induces apoptosis, decreases invasiveness, and downregulates VEGF secretion by activating AMPK signaling in pancreatic cancer cells [Corrigendum]Ye T, Su J, Huang C, et al. OncoTargets Ther. 2016;9:7481â 7492.The authors have advised that a number of errors were made in some of the figures within their paper.Read the original article
OGT-2115 is a heparanase inhibitor (IC50 = 0.4 μM). Heparanase inhibitors suppress breast cancer cell invasion and migration induced by ER stress, and provide a strong rationale for the development of heparanase-based therapeutics for the prevention of metastasis induced by chemotherapeutic reagents.
Analysis of extracellular matrix degradation systems has led to the insight that in cancer invasion there is often crucial interplay between cancer cells and several types of surrounding non-neoplastic stromal cells. Likewise, in normal tissue remodeling processes, the synthesis of proteolytic compo …
EXTERNAL SPEAKER. Dr Sara Rossana Zanivan, Senior Lecturer, Beatson Institute for Cancer Research, University of Glasgow. "Pro-invasive tumour-stroma interactions:thekey role of cancer associated fibroblasts". Hosted in room C1071 C Floor South Block Queens Medical Centre and dual broadcast to The Staff Room Academic Oncology 1st Floor above South Entrance City Hospital. This forms part of the Division of Cancer & Stem Cells seminar series ...
Research Topics, Genomes and Genes, Species, Research Grants, Publications about Control of lung cancer invasion and metastasis by vimentin
Effect of TGFβ1 on the phenotype, migratory ability, and survival of CD16− monocytes. PBMCs were depleted of CD16+ cells using miniMACS magnetic selection. T
CONCLUSIONS: The circular RNA hsa_circ_0091017 can inhibit the proliferation, migration and invasiveness of BCa cells by regulating the expression of microRNA-589-5p. PMID: 31957821 [PubMed - in process]...
Invasion was calculated employing BioCoat MatriGel Invasion Chambers (BD Biosciences) in accordance to the manufacturers recommendations. The upper insert
Most noticeable on CEATEC Japan for those of us who dont live in Japan was a host of robotic and sensor products programmed to talk, think, and behave like Japanese people, mirroring Japanese sensibilities, preferences, and habits.
Ent survival. However, tumor invasion and metastasis contribute to the great majority of breast Tubastatin A supplier cancer deaths. Our efforts towards the
The KOMP Repository Collection is located at the MMRRC at the University of California, Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
Its the zombie-slaying survival game with JRPG elements you didnt know you wanted! Get swarmed by zombies in active-time battles, search for other survivors, eat and most importantly: SURVIVE!
Invasion of the Bunny Snatchers: The Return is a 1995 short subject which is directed by Greg Ford, Terry Lennon and Martin Gates. This is a Sequel to Invasion of the Bunny Snatchers.
The available database information concerning Rab17 and its interactors is insufficient to infer potential effectors and pathways through which this GTPase acts to suppress cancer invasiveness and progression. We, therefore, determined the Rab17 interactome and its influence on the cellular proteome in an unbiased manner. The use of high-accuracy MS-based approaches has enabled us to do this and to show that Rab17 has a close physical and functional relationship with the SNARE protein Vamp8. Rab GTPases are known to recruit specific effector proteins that bind to SNAREs, giving specificity to vesicle fusion (Angers and Merz, 2011). Nevertheless, to our knowledge, our study is the first to provide an indication that the stability and cellular levels of a SNARE protein may be controlled by a Rab GTPase. Moreover, because Vamp8 is the only component of the proteome that is significantly altered following Rab17 knockdown, the relationship between this GTPase and Vamp8 stability is likely to be ...
BACKGROUND/PURPOSE:The effects of chemical and physical interactions in the microenvironment of solid tumors have not been fully elucidated. We hypothesized that acidosis, hypoxia, and elevated interstitial fluid pressure (eIFP) have additive effects on tumor cell biology and lead to more aggressive behavior during tumor progression. We investigated this phenomenon using 3 human osteosarcoma cell lines and a novel in vitro cell culture apparatus. MATERIALS AND METHODS:U2OS, SaOS, and MG63 cell lines were cultured in media adjusted to various pH levels, oxygen tension (hypoxia 2% O2, normoxia 20% O2), and hydrostatic gauge pressure (0 or 50 mm Hg). Growth rate, apoptosis, cell cycle parameters, and expression of mRNA for proteins associated with invasiveness and tumor microenvironment (CA IX, VEGF-A, HIF-1A, MMP-9, and TIMP-2) were analyzed. Levels of CA IX, HIF-1α, and MMP-9 were measured using immunofluorescence. The effect of pH on invasiveness was evaluated in a Matrigel chamber assay.RESULTS:
TY - JOUR. T1 - Cervical carcinoma with full-thickness stromal invasion. T2 - Efficacy of dynamic MR imaging in the assessment of parametrial involvement. AU - Iwata, Sumiyo. AU - Joja, Ikuo. AU - Okuno, Keiko. AU - Miyagi, Yasunari. AU - Sakaguchi, Yukiyoshi. AU - Kudo, Takafumi. AU - Hiraki, Yoshio. PY - 2002/9/1. Y1 - 2002/9/1. N2 - The purpose of this study was to investigate the efficacy of dynamic MR imaging in the assessment of parametrial involvement by cervical carcinoma with full-thickness stromal invasion on thinsection oblique axial T2-weighted images. Dynamic MR images of 24 patients with cervical carcinoma with full-thickness stromal invasion on thin-section oblique axial T2-weighted images were evaluated with pathologic correlation. Dynamic MR imaging was performed using a turboFLASH, 3D-FISP, or 2D-FLASH technique. The imaging planes of dynamic MR imaging were oblique axial planes of the uterine cervix. Dynamic MR imaging was performed twice, once for the early phase (40 to 60 ...
In addition to its well-established role in embryo development, epithelial-to-mesenchymal transition (EMT) has been proposed as a general mechanism favoring tumor metastatization in several epithelial malignancies. Herein, we review the topic of EMT in cholangiocarcinoma (CCA), a primary liver cancer arising from the epithelial cells lining the bile ducts (cholangiocytes) and characterized by an abundant stromal reaction. CCA carries a dismal prognosis, owing to a pronounced invasiveness and scarce therapeutic opportunities. In CCA, several reports indicate that cancer cells acquire a number of EMT biomarkers and functions. These phenotypic changes are likely induced by both autocrine and paracrine signals released in the tumor microenvironment (cytokines, growth factors, morphogens) and intracellular stimuli (microRNAs, oncogenes, tumor suppressor genes) variably associated with specific disease mechanisms, including chronic inflammation and hypoxia. Nevertheless, evidence supporting a complete EMT of
Pancreatic ductal adenocarcinoma (PDAC) and other pancreatic neoplasms exhibited increased SPARCL1 mRNA levels compared to those of the normal pancreas. SPARCL1 mRNA levels were low to absent in microdissected and cultured pancreatic cancer cells, and promoter demethylation increased SPARCL1 levels only slightly in three of eight cell lines. SPARCL1 was observed in small capillaries in areas of inflammation/tumor growth and in some islet cells. In PDAC, 15.4% of vessels were SPARCL1-positive. In contrast, the percentage of SPARCL1-positive vessels was higher in chronic pancreatitis and benign and borderline pancreatic tumors. Recombinant SPARCL1 inhibited pancreatic cancer cell invasion and exerted moderate growth-inhibitory effects. In conclusion, SPARCL1 expression in pancreatic tissues is highly correlated with level of vascularity. Its anti-invasive effects and reduced expression in metastasis indicate tumor-suppressor function ...
Epithelial cell adhesion molecule (EpCAM) is a 40-kD cell-surface glycoprotein that is dramatically overexpressed in the majority of breast cancers. We were the first to demonstrate that EpCAM is directly involved in the regulation of breast cancer migration and invasion. Specifically, in loss-of-function studies we have demonstrated that specific ablation of EpCAM expression: (1) decreases breast cancer invasion in vitro and in vivo; (2) is associated with cytoskeletal rearrangement and alterations in Rho GTPases; and (3) impacts on the expression of transcription factors and genes known to be involved in breast cancer invasion. The hypothesis is that EpCAM plays a central role in the regulation of breast cancer invasion. We are currently exploring this hypothesis in detail using cultured human breast cancer cells, breast cancer xenografts, human breast specimens, and a transgenic mouse model of breast carcinogenesis. Specific aims include (1) Test the hypothesis that EpCAM plays a central role ...
Real‐time imaging. Cells were seeded in a Lab‐Tek Chambered #1.0 Borosilicate Coverglass System (Nalgene Nunc International, Rochester, NY, USA) and were mounted on a Zeiss Axiovert 200M microscope for live‐cell imaging (5% CO2; 37°C) for 2-14 h. Phase‐contrast images were captured every 2 min using a Photometics Coolsnap CCD camera (Scientific, Tuscon, AZ, USA). Images were processed using the Metamorph software (Universal imaging, Downington, PA, USA). Several protrusions was scored by off‐line analysis of the generated videos and plotted as means±s.e.m. For real‐time fluorescence imaging, cells were placed on a Leica SP5 inverted microscope equipped with a × 63 1.3NA glycerol objective. Cells were maintained in Leibovitz‐15‐buffered medium (Invitrogen, Breda, The Netherlands) at 37°C in a climate chamber.. Invasion assay. For in vitro invasion assays, 24‐well BioCoat matrigel invasion chambers (#354480, BD Biosciences, Alphen aan den Rijn, The Netherlands) were used ...
Strongylophorine-26, a new meroditerpenoid, was recently identified as an inhibitor of cancer cell invasion. This study was undertaken to characterize its mechanism of action. We find that strongylophorine-26 inhibits the motility of MDA-MB-231 breast carcinoma cells on a plastic surface. Upon addition of strongylophorine-26, rapid cell contraction and depolarization occurred, followed by spreading and flattening of the entire cell. Treated cells exhibited increased membrane ruffling throughout and extended lamellipodia in all directions. Strongylophorine-26 induced a decrease in actin stress fibers, a dramatic increase in the size and number of focal adhesions, and the appearance of a dense meshwork of actin filaments around the cell periphery. Strongylophorine-26 caused a transient activation of the small GTPase Rho and treatment with the Rho inhibitor C3 exoenzyme abrogated the anti-invasive activity of strongylophorine-26. These effects are distinct from those of many motility and ...
Effective anti‐tumour immune response requires appropriate recruitment and activation of immune cells. However, despite expression of tumour antigens in most tumours, including bladder tumours (Nishiyama et al, 2001; Sharma et al, 2003), escape from T‐cell immunity is more often the rule rather than an exception. In this study, we examined and compared the immune response going on during development of bladder tumours induced by two cell lines: MB49 and its more invasive variant MB49‐I. Our analysis of adaptive immune response during MB49 and MB49‐I development and exploration of molecules secreted by both tumours showed that MB49‐I has developed two mechanisms to acquire invasion properties: loss of putative tumour antigens and overexpression of decorin.. The expression of the male transplantation H‐Y antigens by MB49 was shown to induce an anti‐tumour immune response when injected in female mice (Halak et al, 1999). Our results showed that, in stark contrast to MB49, MB49‐I has ...