Tumor-bone interactions in skeletal metastasis.

Bone metastases are a frequent clinical problem in patients with breast, prostate, and other cancers. Formation of these lesions is a site-specific process determined by multiple cellular and molecular interactions between the cancer cells and the bone microenvironment. Clinical studies, and in vivo and in vitro experimental approaches, have been useful to dissect different stages of this process. Mechanisms identified as relevant to cancer spreading and tumoral growth in the bones include (a) early vascular spread of cancer cells to bones; (b) adhesion of cancer cells to the bone microvasculature and matrix components; (c) presence of growth factors and chemo-attractants in bone; (d) osteolysis by osteoclasts, tumor associated macrophages, and cancer cells; and (e) tumor-induced local osteoblastic proliferation. Although none of these mechanisms alone are responsible for the development of bone metastases, their investigation may lead to novel therapeutic approaches that specifically block these stages and, thus, may hinder development of bone metastasis. The use of bisphosphonates and other experimental strategies already is being tested in clinical trials.