Metastasis suppressor CC3 inhibits angiogenic properties of tumor cells invitro

Resistance to apoptosis and ability to promote angiogenesis are integral fe atures of the metastatic phenotype. Human gene CC3 is a metastasis suppress or for variant small cell lung carcinoma and a mouse melanoma in vivo. We h ave shown previously that metastasis-suppressing function of CC3 might be d ue at least in part to the ability of CC3 protein to predispose tumor cells to apoptosis, Here we demonstrate that CC3 has a previously unidentified e ffect on the ability of tumor cells to induce angiogenesis in vitro. Expres sion of CC3 in three different tumor cell lines significantly diminished th eir angiogenic character as manifested in the in vitro proliferation and mi gration assays with endothelial cells of both macro- and microvascular orig in. Expression of CC3 induced changes in RNA levels of several angiogenic m odulators consistent with the overall reduction in angiogenic properties. T hese results indicate that expression of CC3 has a dual effect on phenotype of tumor cells ultimately inhibiting their metastatic potential.