MECHANISMS INVOLVED IN THE METASTASIS OF CANCER TO BONE

The metastasis of cancer to bone is a frequent outcome of common malignancies and is often associated with significant morbidity due to osteolysis. Bone metastasis is also selective in that a disproportionately small number of malignancies account for the majority of tumors which spread to bone. While the mechanisms of bone destruction have been studied, those responsible for the site-specific nature of bone metastasis are poorly understood. As a metastatic target, bone is unique in that it is continuously being remodelled under the influence of local and systemic growth factors, many of which are embedded in the bone matrix. This review summarizes evidence for the hypothesis that the formation of metastatic tumors in bone is the consequence of a unique microenvironment where metastatic cells can alter the metabolism of bone, thereby regulating the release of soluble bone-derived growth factors as a consequence of bone resorption. These, in turn, can modulate the malignant phenotypic properties of receptive cells. Transforming growth factor-beta is one factor which can promote the growth and motility of Walker 256 cells, a rat cell line with a propensity to metastasize spontaneously to bone.