• Circulating osteoprotegerin (OPG), a member of the receptor activator of nuclear factor kappa-B (RANK) axis, may influence breast cancer risk via its role as the decoy receptor for both the RANK ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). (biomedcentral.com)
  • Measured by its ability to inhibit Fas Ligand-induced apoptosis of Jurkat human acute T cell leukemia cells. (bio-techne.com)
  • Among TNF family members, DcR3 was shown to bind with Fas ligand (FasL) and LIGHT and inhibit FasL- and LIGHT-induced apoptosis. (bio-techne.com)
  • Thus, in addition to DcR1, DcR2 and OPG, DcR3 is another TNFR family molecule which modulates ligands that induce apoptosis. (bio-techne.com)
  • Cell death occurs under physiological and pathological conditions and mediates through three pathways as follows: apoptosis, autophagic cell death, and necrosis. (biomedcentral.com)
  • In contrast to necrosis (murdered cells), in apoptosis (commit suicide) and autophagy process, cytoplasmic membranes are maintained and cell body is completely removed without any inflammation. (biomedcentral.com)
  • However, if phagocytosis of the cell does not occur at the final stage of apoptosis or autophagic process, the cells are removed through secondary necrosis [ 12 ]. (biomedcentral.com)
  • Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) binds to death receptors and induces apoptosis in various cancer cell lines while sparing normal cells. (oncotarget.com)
  • More recent data show that OPG is also produced in breast tumor cells, and that it can promote tumor growth and metastasis [ 5 , 6 ]. (biomedcentral.com)
  • Tumor cells can induce, through exposition of amyloid precursor protein (APP), DR6-mediated endothelial cell necroptosis allowing tumors metastasis. (wikidoc.org)
  • However, there is no single animal model that ideally replicates the entire metastatic process from primary breast tumor to bone metastasis. (biomedcentral.com)
  • Bone homeostasis is maintained by the interplay between the receptor activator of nuclear factor kappa-B (RANK), its soluble activation ligand (RANKL), and OPG. (biomedcentral.com)
  • Receptor activator of nuclear factor κ B (RANK), also known as TRANCE receptor or TNFRSF11A, is a member of the tumor necrosis factor receptor (TNFR) molecular sub-family. (wikipedia.org)
  • RANKL (receptor activator for nuclear factor κ B ligand) is found on the surface of stromal cells, osteoblasts, and T cells. (wikipedia.org)
  • RANK is the receptor for RANK-Ligand (RANKL) and part of the RANK/RANKL/OPG signaling pathway that regulates osteoclast differentiation and activation. (wikipedia.org)
  • Osteoprotegerin (OPG) is a decoy receptor for RANKL, and regulates the stimulation of the RANK signaling pathway by competing for RANKL. (wikipedia.org)
  • Unlike other members of the TNFSF, each surface interaction in RANK-RANKL is continuous. (wikipedia.org)
  • This system is balanced by the relative expression of OPG to RANKL, which are highly regulated by many factors including hormones, immune signals, and growth factors. (wikipedia.org)
  • The balance between RANKL and OPG is a target for therapy in many diseases including estrogen deficiency-associated osteoporosis, rheumatoid arthritis, Paget's disease, periodontal disease, and bone tumors and malignancies. (wikipedia.org)
  • Once the tumor is seeded in the bone, the tumor cells stimulate bone resorption by secreting factors such as RANKL or prompting the surrounding stroma to express growth factors. (wikipedia.org)
  • They are now the treatment of choice in tumour-induced hypercalcaemia, and they can reduce bone pain and skeletal complications such as pathological fractures. (biomedcentral.com)
  • Tumour cells in the bone marrow cavity secrete a variety of paracrine factors that stimulate bone formation. (biomedcentral.com)
  • These metastases are predominantly osteolytic and develop when tumor cells interact with bone. (biomedcentral.com)
  • Previously, we developed a mouse model of tumor-bone interaction in which three mouse breast cancer cell lines were implanted onto the calvaria. (biomedcentral.com)
  • Analysis of tumors from this model revealed that they exhibited strong bone resorption, induction of osteoclasts and intracranial penetration at the tumor bone (TB)-interface. (biomedcentral.com)
  • Furthermore, these treatment methods have limited efficacy due in part to the fact that they do not effectively target the interaction between tumor cells and bone [ 5 ]. (biomedcentral.com)
  • Even though the bisphosphonate class of drugs (which target the tumor-bone interface) have been shown to improve the quality of life and disease-free survival in some patients, more therapeutic targets and agents are desirable [ 6 ]. (biomedcentral.com)
  • Within the osteolytic lesions of bone metastases, tumor cells interact with osteoclasts (bone resorbing cells) and osteoblasts (bone forming cells), thereby inhibiting normal bone development and ultimately leading to bone destruction [ 1 - 4 ]. (biomedcentral.com)
  • and bone morphogenetic proteins, BMPs) that stimulate tumor growth and bone destruction [ 1 ]. (biomedcentral.com)
  • Dairy supplementation increased serum insulin-like growth factor I concentrations (19.89 nmol/L) and reduced concentrations of urinary deoxypyridinoline (-1.78 nmol/mmol creatinine) and serum parathyroid hormone (-10.46 pg/mL) but did not significantly affect the serum concentrations of osteocalcin, bone alkaline phosphatase, and C-terminal telopeptide of type 1 collagen. (bvsalud.org)
  • Like osteoprotegerin (OPG), DcR3 lacks a transmembrane sequence and is a secreted protein. (bio-techne.com)
  • TRAIL (also known as Apo2 ligand), is a trimeric protein, a TNF superfamily member, expressed as a type-II transmembrane protein and plays a physiological role in anti-tumor immune surveillance [ 1 - 6 ]. (oncotarget.com)
  • Human decoy receptor 3 (DcR3), also called TNFRSF6B, TR6 and M68, is a member of the TNF receptor superfamily. (bio-techne.com)
  • Like other members of the TNFR family, it has four extracellular cysteine-rich pseudo-repeat domains (CRDs). (wikipedia.org)
  • RANK contains four CRDs spanning a length of 100 Angstroms which makes it the longest member of the TNFR family to date. (wikipedia.org)
  • Overexpression of DcR3 might be a mechanism by which certain tumors escape immune-cytotoxic attack. (bio-techne.com)
  • The protein encoded by this gene is a member of the TNF-receptor superfamily. (wikidoc.org)
  • [2] The DR6 is an alpha-helical integral membrane receptor protein that shows evidence that it has something to do with the inhibition of blood vessels forming on tumors which would allow them to grow larger. (wikidoc.org)
  • [8] APP ( amyloid precursor protein ) is the natural ligand of DR6 and is first cleaved into Aβ and N-APP. (wikidoc.org)
  • In an HCT116 xenograft model ADI-TRAIL localized to the tumor and induced dose-dependent tumor regression, the fusion protein was superior to rhTRAIL administered at the same molar amounts. (oncotarget.com)
  • As it is presented in this schematic presentation, HC composing connexon placing on the body of osteocytes and osteoblasts respond to different signals which then control the transmission of different factors among are PGE2, ATP, and PNS. (biomedcentral.com)
  • This study observed reduced breast cancer risk among women with comparatively high OPG concentrations, but given a small number of incident cases ( n = 76), risk by tumor subtypes (e.g., by estrogen (ER) and progesterone (PR) receptor status) was not investigated. (biomedcentral.com)
  • Traditionally recognized risk factors for osteoporosis include white race, low body weight, estrogen or androgen deficiency, calcium and/or vitamin D deficiency, and thyroid hormone excess. (medscape.com)
  • TRAF6 stimulates the activation of the c-jun N-terminal kinase (JNK) and nuclear factor kappa-b (NF-κB) pathways which trigger differentiation and activation of osteoclasts. (wikipedia.org)
  • Death receptor 6 ( DR6 ), also known as tumor necrosis factor receptor superfamily member 21 ( TNFRSF21 ), is a cell surface receptor of the tumor necrosis factor receptor superfamily which activates the JNK and NF-κB pathways. (wikidoc.org)
  • The free serum levels of this DR6 are heightened with anti-cell death factors in patients that have later stage ovarian cancer. (wikidoc.org)
  • It was found to be expressed in a variety of different tissues and at high levels in many malignant tumors. (bio-techne.com)
  • The EPIC cohort was designed to identify risk factors for cancer [ 13 ]. (biomedcentral.com)
  • In addition to these traditional risk factors, other risk factors are associated with solid organ transplantation. (medscape.com)
  • Receptor activator of nuclear factor κ B (RANK), also known as TRANCE receptor or TNFRSF11A, is a member of the tumor necrosis factor receptor (TNFR) molecular sub-family. (wikipedia.org)
  • It has been shown that some pro-inflammatory cytokines could possess osteoclastogenic and/or anti-osteoclastogenic properties and can target osteoclasts directly or via receptor activator of nuclear factor κB (RANK)/RANK ligand(RANKL)/osteoprotegerin (OPG) system. (biochemia-medica.com)
  • Many oncogenes (RAS, PI3K, KIT) and tumor suppressors (P53, RB, PTEN) are frequently mutated in different human malignancies. (medscape.com)
  • However, unlike other hematologic malignancies diffusely infiltrating the marrow, it behaves like a tumor metastasis with the involvement of the bone. (tmeresearch.org)
  • Tumor Microenviron [serial online] 2018 [cited 2023 Dec 3];1:1-8. (tmeresearch.org)
  • 15. The combinations of polymorphisms in vitamin D receptor, osteoprotegerin and tumour necrosis factor superfamily member 11 genes are associated with bone mineral density. (nih.gov)
  • High throughput genome sequencing of tumor DNA has elucidated low-frequency mutations in several genes that are highly likely to drive oncogenesis. (medscape.com)
  • Following successful antigen-specific activation in secondary lymphoid tissues, T cells begin to produce numerous pro-inflammatory cytokines such as interleukin (IL)-2, -4, -5, -6 and -8, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), granulocyte-macrophage colony stimulating factor (GM-CSF), interferon γ (IFN-γ), etc. (3). (biochemia-medica.com)
  • Final common mediators of disease, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, are well studied and have yielded breakthrough therapeutics. (frontiersin.org)
  • Epithelial cell rests of Malassez (ERM) are integrated in the periodontal ligament and have been found to secrete several growth factors, cytokines, chemokines, adhesion molecules and associated proteins. (scielo.org.za)
  • 10] Interestingly, breast basal-like tumors shared a number of molecular characteristics common to ovarian cancer such as the types and frequencies of genomic mutations, suggesting a related etiology and potentially similar responsiveness to some of the same therapies. (medscape.com)
  • In addition, the BM microenvironment may also be divided into the cellular compartment, comprised of hematopoietic cells and nonhematopoietic cells and the noncellular compartment where the extracellular matrix (ECM), cytokines and growth factors are present. (tmeresearch.org)
  • Additionally, autoantibodies to rheumatoid factor (RF) and citrullinated protein are often present. (frontiersin.org)
  • These cellular processes are self-sufficiency in growth signals (oncogene addiction), insensitivity to growth-inhibitory signals (loss of tumor suppressors), evading programmed cell death (anti-apoptosis), limitless replication potential (aberrant cell cycle), sustained angiogenesis, and invasion/metastasis. (medscape.com)
  • 7, 8, 9] The Cancer Genome Atlas Network analyzed the somatic mutation spectrum of four mRNA-expression subtypes of breast tumors, and found that basal-like tumors differed substantially from luminal A, luminal B and HER2- enriched tumors. (medscape.com)
  • 3] Each of these 6 acquired physiologic capabilities occurs during tumor development because of reactivation and changing of existing cellular programs utilized during embryogenesis and development. (medscape.com)
  • The maladaptive nature of myeloma PCs and the BM microenvironment niche has been recognized to play a crucial role in the pathogenesis and progression of the disease which behaves in a manner similar to solid tumors in their growth and dissemination. (tmeresearch.org)
  • Like other members of the TNFR family, it has four extracellular cysteine-rich pseudo-repeat domains (CRDs). (wikipedia.org)
  • Somatic mutations vary in distinct cancer types (eg, brain, pancreas, breast, colon), as well as in a given tumor type, but they do appear to utilize common overlapping oncogenic pathways detected in the malignant phenotype. (medscape.com)