Breast Cancer Research and Treatment

, Volume 92, Issue 3, pp 207–215 | Cite as

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

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


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.

Key words

apoptosis breast cancer OPG survival TRAIL 



epidermal growth factor




receptor activator of nuclear factor κB ligand


tumour growth factor


tumour necrosis factor


tumour necrosis factor related apoptosis inducing ligand


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Copyright information

© Springer 2005

Authors and Affiliations

  • Ingunn Holen
    • 1
    • 3
  • Simon S. Cross
    • 1
  • Helen L. Neville-Webbe
    • 1
  • Neil A. Cross
    • 1
    • 2
  • Sabapathy P. Balasubramanian
    • 2
  • Peter I. Croucher
    • 1
    • 2
  • C. Alyson Evans
    • 1
  • Jennifer M. Lippitt
    • 1
    • 2
  • Robert E. Coleman
    • 1
  • Colby L. Eaton
    • 1
    • 2
  1. 1.Bone Oncology Group, Division of Genomic MedicineUniversity of SheffieldUK
  2. 2.Division of Clinical Sciences South, School of Medicine and Biomedical SciencesUniversity of SheffieldUK
  3. 3.Clinical Oncology, Genomic Medicine, School of Medicine and Biomedical SciencesUniversity of SheffieldSheffieldUK

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