Osteoprotegerin (OPG) expression by breast cancer cells in vitro and breast tumours in vivo - a role in tumour cell survival?

HOLEN, Ingunn, CROSS, Simon S, NEVILLE-WEBBE, Helen L, CROSS, Neil A, BALASUBRAMANIAN, Sabapathy P, CROUCHER, Peter I, EVANS, C Alyson, LIPPITT, Jennifer M, COLEMAN, Robert E and EATON, Colby L (2005). Osteoprotegerin (OPG) expression by breast cancer cells in vitro and breast tumours in vivo - a role in tumour cell survival? Breast Cancer Research and Treatment, 92 (3), 207-15.

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Link to published version:: https://doi.org/10.1007/s10549-005-2419-8


In addition to its role in bone turnover, osteoprotegerin (OPG) has been reported to bind to and inhibit Tumour necrosis factor-related apoptosis inducing ligand (TRAIL). TRAIL is produced in tumours by invading monocytes, inducing apoptosis in neoplastic cells sensitive to this cytokine. OPG production by tumour cells would therefore be a novel mechanism whereby cancer cells evade host defences and gain a growth advantage. In this study we show that OPG produced by breast cancer cells enhances tumour cell survival by inhibiting TRAIL-induced apoptosis. OPG expression by breast cancer cells (MDA-MB 436/231) grown in vitro was examined using PCR and ELISA, and the sensitivity of these cells to TRAIL was determined. The effects of OPG on TRAIL induced apoptosis was investigated by exposing MDA-MB 436 cells to TRAIL, in the presence or absence of OPG, followed by assessment of nuclear morphology. We found that the levels of OPG produced were sufficient to inhibit TRAIL-induced apoptosis, suggesting that OPG may play a role in tumour cell survival. We also examined the expression pattern of OPG in a selection of breast tumours (n=400) by immunohistochemistry, and related OPG expression to the clinico-pathological data for each tumour. OPG expression was found to be negatively correlated with increasing tumour grade. To our knowledge these results are the first to demonstrate that OPG can act as an endocrine survival factor for breast cancer cells, as well as reporting the expression patterns of OPG in a large cohort of human breast tumours.

Item Type: Article
Research Institute, Centre or Group - Does NOT include content added after October 2018: Biomedical Research Centre
Identification Number: https://doi.org/10.1007/s10549-005-2419-8
Page Range: 207-15
Depositing User: Jamie Young
Date Deposited: 02 Jun 2015 15:50
Last Modified: 18 Mar 2021 18:45
URI: https://shura.shu.ac.uk/id/eprint/9975

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