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• W1599072092 abstract "Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor ᴋB (RANK) and RANK ligand (RANKL), are members of the tumour necrosis factor receptor superfamily (TNFRSF), signal transducers which have pleiotropic actions. Each family member has unique structural attributes shown to couple them directly to specific signalling pathways involved in cell proliferation, differentiation and survival. Previous studies have clinically correlated OPG, RANK and RANKL expression, at both transcript and protein levels, with increasing cancer tumour burden, metastatic bone involvement and androgen status, however the mechanisms by which these molecules exert their effects remain elusive. This study aimed to establish what influence targeting OPG, RANK and RANKL expression may have on osteotrophic prostate and breast cancer cells in vitro and to subsequently explore the effect(s) Hepatocyte Growth Factor (HGF) and Bone Matrix Extract (BME) might also exert on cancer cell behaviour following manipulation of these molecules.The current study utilised 2 prostate cancer cell lines with varying androgen status, metastatic potential and bone metastasis phenotypes. Initial screening showed that the more aggressive osteolytic PC-3 cells expressed OPG, whilst weakly metastatic mixed-osseous LNCaP cells had very low expression. Whilst RANK was present in both cell lines, RANKL expression was only detected in the LNCaP cells. Reduction of OPG expression in the PC-3 cells resulted in increased cell invasion in vitro, which was further enhanced when treated with BME. No other cellular traits were affected by targeting OPG directly, however, cell migration was enhanced when the manipulated cells were exposed to the representative bone microenvironment. In contrast the addition of a recombinant form of OPG to LNCaP cells resulted in decreased cell invasion, a trend which was reversed when combined with BME. Combination of OPG and BME treatment reduced the migratory response of LNCaP cells, whilst combination of OPG and HGF were pro-migratory. The targeting of RANK in PC-3 cells affected cell proliferation and matrix adhesion in vitro though the addition of HGF or BME appeared to have no further direct influence on these manipulated cells. Targeting of the RANKL expression with a neutralising monoclonal antibody had little effect on cancer cell behaviour; however combined exposure with HGF or BME resulted in similar behaviour patterns seen under the OPG treatments.In our breast cancer cohort, RANK and RANKL expression were correlated with bone metastases and survival rates. Though OPG did not appear to be associated with grading, data also implied a role in overall survival. In the aggressive osteolytic MDA-MB-231 breast cancer cells, reduced OPG expression resulted in increased motility and invasion, traits which were little affected upon exposure to HGF or BME. In contrast the targeting of RANK expression in MDA-MB-231 cells resulted in reductions in all the cancer cell behaviours studied, but again these appeared unaffected under the influence of HGF or BME.The complexity of the bone environment underpins the vast number of soluble factors, signalling pathways and transcription regulators which can influence osteotrophic cancer cells. As indicated by the licensing of Denosumab, one therapeutic approach is not suitable for all osteotrophic cancers. Therefore further elucidation into the intricacies of these interactions is needed." @default.
• W1599072092 created "2016-06-24" @default.
• W1599072092 creator A5015057915 @default.
• W1599072092 date "2014-01-01" @default.
• W1599072092 modified "2023-09-27" @default.
• W1599072092 title "The role of osteoprotegerin and receptor activator of nuclear factor ᴋb in osteotropic prostate and breast cancers" @default.
• W1599072092 cites W106733404 @default.
• W1599072092 cites W117902596 @default.
• W1599072092 cites W1274170188 @default.
• W1599072092 cites W128880540 @default.
• W1599072092 cites W144340857 @default.
• W1599072092 cites W1451341926 @default.
• W1599072092 cites W1493707677 @default.
• W1599072092 cites W1496143836 @default.
• W1599072092 cites W1509251446 @default.
• W1599072092 cites W1520049468 @default.
• W1599072092 cites W1520425169 @default.
• W1599072092 cites W1526016744 @default.
• W1599072092 cites W153206471 @default.
• W1599072092 cites W1533247917 @default.
• W1599072092 cites W1541480589 @default.
• W1599072092 cites W1541516070 @default.
• W1599072092 cites W1545381643 @default.
• W1599072092 cites W1545561369 @default.
• W1599072092 cites W1548818293 @default.
• W1599072092 cites W1552645317 @default.
• W1599072092 cites W1553178519 @default.
• W1599072092 cites W1553431928 @default.
• W1599072092 cites W1555159013 @default.
• W1599072092 cites W1555589113 @default.
• W1599072092 cites W1563832763 @default.
• W1599072092 cites W1564427947 @default.
• W1599072092 cites W1576773659 @default.
• W1599072092 cites W1580523172 @default.
• W1599072092 cites W1587842942 @default.
• W1599072092 cites W1604468403 @default.
• W1599072092 cites W1605709431 @default.
• W1599072092 cites W1626663099 @default.
• W1599072092 cites W164274307 @default.
• W1599072092 cites W1649526546 @default.
• W1599072092 cites W1650001464 @default.
• W1599072092 cites W1672290086 @default.
• W1599072092 cites W170447056 @default.
• W1599072092 cites W1753444805 @default.
• W1599072092 cites W1761343402 @default.
• W1599072092 cites W181281151 @default.
• W1599072092 cites W1815541658 @default.
• W1599072092 cites W1828456061 @default.
• W1599072092 cites W1878980538 @default.
• W1599072092 cites W1899740218 @default.
• W1599072092 cites W1938617858 @default.
• W1599072092 cites W1943507320 @default.
• W1599072092 cites W1944909911 @default.
• W1599072092 cites W1945133566 @default.
• W1599072092 cites W1963917229 @default.
• W1599072092 cites W1964066819 @default.
• W1599072092 cites W1966743015 @default.
• W1599072092 cites W1966970126 @default.
• W1599072092 cites W1967990571 @default.
• W1599072092 cites W1968302410 @default.
• W1599072092 cites W1969670678 @default.
• W1599072092 cites W1971027103 @default.
• W1599072092 cites W1971694540 @default.
• W1599072092 cites W1971949613 @default.
• W1599072092 cites W1972287875 @default.
• W1599072092 cites W1974140746 @default.
• W1599072092 cites W1974698602 @default.
• W1599072092 cites W1975577875 @default.
• W1599072092 cites W1976883684 @default.
• W1599072092 cites W1977013832 @default.
• W1599072092 cites W1978198656 @default.
• W1599072092 cites W1978881929 @default.
• W1599072092 cites W1979136607 @default.
• W1599072092 cites W1979349240 @default.
• W1599072092 cites W1979759722 @default.
• W1599072092 cites W1980660707 @default.
• W1599072092 cites W1980727670 @default.
• W1599072092 cites W1980839772 @default.
• W1599072092 cites W1981266896 @default.
• W1599072092 cites W1981361007 @default.
• W1599072092 cites W1982895658 @default.
• W1599072092 cites W1983514189 @default.
• W1599072092 cites W1984433201 @default.
• W1599072092 cites W1984455034 @default.
• W1599072092 cites W1984673297 @default.
• W1599072092 cites W1985550922 @default.
• W1599072092 cites W1986201328 @default.
• W1599072092 cites W1986471913 @default.
• W1599072092 cites W1986714144 @default.
• W1599072092 cites W1986819031 @default.
• W1599072092 cites W1988079149 @default.
• W1599072092 cites W1988594450 @default.
• W1599072092 cites W198934061 @default.
• W1599072092 cites W1989607165 @default.
• W1599072092 cites W1990261637 @default.
• W1599072092 cites W1994596418 @default.
• W1599072092 cites W1995168398 @default.
• W1599072092 cites W1995579100 @default.
• W1599072092 cites W1996388835 @default.
• W1599072092 cites W1997691582 @default.

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