Role of osteoprotegerin (OPG) in cancer.
OPG (osteoprotegerin), a secreted member of the TNF (tumour necrosis factor) receptor superfamily, has a variety of biological functions which include the regulation of bone turnover. OPG is a potent inhibitor of osteoclastic bone resorption and has been investigated as a potential therapeutic for the treatment of both osteoporosis and tumour-induced bone disease. Indeed, in murine models of cancer-induced bone disease, inhibition of osteoclastic activity by OPG was also associated with a reduction in tumour burden. The discovery that OPG can bind to and inhibit the activity of TRAIL (TNF-related apoptosis-inducing ligand) triggered extensive research into the potential role of OPG in the regulation of tumour cell survival. A number of reports from studies using in vitro models have shown that OPG protects tumour cells from the effects of TRAIL, thereby possibly providing tumour cells that produce OPG with a survival advantage. However, the ability of OPG to act as a tumour cell survival factor remains to be verified using appropriate in vivo systems. A third area of interest has been the use of OPG as a prognostic marker in various cancer types, including myeloma, breast and prostate cancer. This review provides an overview of the role of OPG in cancer, both in cancer-induced bone disease and in tumour growth and survival.
Holen
Ingunn
I
Academic Unit of Clinical Oncology, School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield S10 2RX, U.K. I.Holen@Sheffield.ac.uk
Shipman
Claire M
CM
D000818:Animals; D017209:Apoptosis; D016723:Bone Remodeling / Q000502:physiology; D001862:Bone Resorption / Q000209:etiology / Q000503:physiopathology; D002470:Cell Survival / Q000502:physiology; D005260:Female; D006023:Glycoproteins / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology* / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology* / Q000627:therapeutic use
D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human