MECHANISMS INVOLVED IN THE METASTASIS OF CANCER TO BONE

The metastasis of cancer to bone is a frequent outcome of common malig nancies and is often associated with significant morbidity due to oste olysis. 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 st udied, those responsible for the site-specific nature of bone metastas is are poorly understood. As a metastatic target, bone is unique in th at it is continuously being remodelled under the influence of local an d systemic growth factors, many of which are embedded in the bone matr ix. This review summarizes evidence for the hypothesis that the format ion of metastatic tumors in bone is the consequence of a unique microe nvironment where metastatic cells can alter the metabolism of bone, th ereby regulating the release of soluble bone-derived growth factors as a consequence of bone resorption. These, in turn, can modulate the ma lignant 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 sp ontaneously to bone.