Are matrix metalloproteinases relevant therapeutic targets for prostate cancer bone metastasis?

After basal and squamous cell skin cancers, prostate cancer is the most frequent cancer in men in the United States, with 186,320 men estimated to be diagnosed with the disease and 28,660 expected to die from it in 2008 1. Approximately 90% of hematogenous metastases in prostate cancer patients occur in bone 2, making skeletal complications the leading cause of morbidity and mortality in these patients. Although skeletal metastases from prostate cancer are usually considered osteoblastic by radiologic analysis, histologic and biochemical studies suggest that osteolytic and osteoblastic responses are sequentially linked 3–5. A vicious cycle in which prostate cancer cells secrete factors that stimulate bone matrix turnover, which in turn releases growth factors that enhance tumour proliferation, has been proposed 6. In the normal bone microenvironment, endosteal cells (osteoblasts, osteoclasts) and bone marrow cells (fibroblasts, pre-osteoblasts, pre-osteoclasts, lymphoid and myeloid cells, endothelial cells, hematopoietic and mesenchymal stem cells) communicate with each other in a homeostatic process that involves transmission of various biologic signals. However, this delicate equilibrium is perturbed when prostate cancer cells colonize the bone, leading to an alteration of the physiologic balance between bone formation and bone resorption, and to a hospitable environment for expansion of the metastases 7. A role for matrix metalloproteinases (MMPs) in bone metastasis has long been suspected. Because MMPs Are matrix metalloproteinases relevant therapeutic targets for prostate cancer bone metastasis?