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Osteoprotegerin (OPG) Expression by Breast Cancer Cells in vitro and Breast Tumours in vivo – A Role in Tumour Cell Survival?

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Summary

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.

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Abbreviations

EGF:

epidermal growth factor

OPG:

osteoprotegerin

RANKL:

receptor activator of nuclear factor κB ligand

TGF:

tumour growth factor

TNF:

tumour necrosis factor

TRAIL:

tumour necrosis factor related apoptosis inducing ligand

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Authors and Affiliations

  1. Bone Oncology Group, Division of Genomic Medicine, University of Sheffield, Sheffield, UK

    Ingunn Holen, Simon S. Cross, Helen L. Neville-Webbe, Neil A. Cross, Peter I. Croucher, C. Alyson Evans, Jennifer M. Lippitt, Robert E. Coleman & Colby L. Eaton

  2. Division of Clinical Sciences South, School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield, UK

    Neil A. Cross, Sabapathy P. Balasubramanian, Peter I. Croucher, Jennifer M. Lippitt & Colby L. Eaton

  3. Clinical Oncology, Genomic Medicine, School of Medicine and Biomedical Sciences, University of Sheffield, Beech Hill Road, S10 2R, Sheffield, UK

    Ingunn Holen

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  1. Ingunn Holen
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  2. Simon S. Cross
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  3. Helen L. Neville-Webbe
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Correspondence to Ingunn Holen.

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Holen, I., Cross, S.S., Neville-Webbe, H.L. et al. Osteoprotegerin (OPG) Expression by Breast Cancer Cells in vitro and Breast Tumours in vivo – A Role in Tumour Cell Survival?. Breast Cancer Res Treat 92, 207–215 (2005). https://doi.org/10.1007/s10549-005-2419-8

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  • DOI: https://doi.org/10.1007/s10549-005-2419-8

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