Osteonectin promotes prostate cancer cell migration and invasion: A possible mechanism for metastasis to bone

The mechanism underlying the "organ-specific" metastasis of prostate cancer cells to the bane is still poorly understood. It is not clear whether the cells only invade the bone and proliferate there or whether they invade man y tissues but survive mainly in the bone ("seed and soil"). Extracts from v arious organs were used as chemoattractants in the irt vitro chemotaxis and invasion assays, Results show that, in comparison with extracts of other t issues, bone extracts promote a 2- to 4-fold increase in chemotaxis by huma n prostate epithelial cells and a 4-fold increase in the invasive ability o f human prostate carcinoma cells. The purified active factor from bone and from marrow stromal-cell-conditioned medium is a low glycosylated osteonect in that specifically promotes the invasive ability of bone-metastasizing pr ostate land breast) cancer cells but not that of non-bone-metastasizing tum or cells. It does not stimulate the growth of prostate cancer cells irt vit ro or in vivo. Because osteonectin specifically enhances matrix metalloprot ease activity in prostate and breast cancer cells land not in other tumor c ell types), we conclude that prostate cancer cell metastasis to the bone is , in part, mediated by the ability of osteonectin to promote migration, pro tease activity, and invasion.