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Role of osteoprotegerin in breast cancer growth
Summary
We identified that osteoprotegerin expression by breast cancers enhances their growth in the breast and bone. We aim to identify how osteoprotegerin enhances tumour growth and the role of stromal cells in this process.
Description
One of the focus areas of the laboratory is the spread of primary cancers to other sites in the body that results in secondary cancer. This process, known as metastasis, is a serious and unfortunately common complication of many cancers including breast cancer, which often spreads to bone.
We have shown that a protein called osteoprotegerin inhibits the process of bone breakdown. Osteoprotegerin is commonly expressed by the bone forming cells, and we provided some of the first evidence that it is also produced by a number of cancers.
We explored the consequences of regulating osteoprotegrin levels in breast cancers and determined that this factor can regulate tumour growth both in bone and in the breast. This identified a new role for this protein and indicated that high levels of osteoprotegerin in a tumour might be a poor prognostic indicator for patients.
We are now determining how this protein affects tumour growth and whether we can counteract its activity
Funding
National Breast Cancer Foundation
Selected Publications
Fisher, J.L., Thomas-Mudge, R.J., Elliott, J., Hards, D.K., Sims, N.A., Slavin, J., Martin, T.J. and Gillespie, M.T. (2006). Osteoprotegerin over-expression by breast cancer cells enhances orthotopic and osseous tumor growth, and contrasts with that delivered therapeutically. Cancer Research. 66, 3620-3628. Reported in The BreastCancer.Net News.4451-4458.
Price, J.T., Quinn, J.M.W., Sims, N.A., Moore, J., Waldeck, K., Docherty, S.E., Myers, D., Nakamura, A., Waltham, M.C., Gillespie, M.T. and Thompson, E.W. (2005). The HSP90 inhibitor, 17-AAG, enhances osteoclast formation and potentiates bone metastasis of a human breast cancer cell line. Cancer Research. 65, 4929-4938.
Jans, D.A., Thomas, R.J. and Gillespie, M.T. (2003). Parathyroid hormone-related protein (PTHrP): a nucleocytoplasmic shuttling protein with distinct paracrine and intracrine roles. In "Vitamins and Hormones", Edited by Gerald Litwack. Elsevier Science, pp. 345-384.
Guise, T.A., Yin, J.J., Thomas, R.J., Dallas, M., Cui, Y. and Gillespie, M.T. (2002). Parathyroid hormone-related protein (PTHrP)-(1-139) isoform is efficiently secreted in vitro and enhances breast cancer metastasis to bone in vivo. Bone. 30, 670-676.
Conlan, L.A., Martin, T.J. and Gillespie, M.T. (2002). The C-terminus of parathyroid hormone-related protein (PTHrP) interacts with b-arrestin 1B. FEBS Letters. 527, 71-75.
Thomas, R.J., Guise, T.A., Yin, J.J., Elliott, J., Horwood, N.J., Martin, T.J., and Gillespie, M.T. (1999). Breast cancer cells interact with osteoblasts to support osteoclast formation. Endocrinology. 140, 4451-4458.