GRO-BETA, GRO-ALPHA -C-X-C- CHEMOKINE, IS AN ANGIOGENESIS INHIBITOR THAT SUPPRESSES THE GROWTH OF LEWIS-LUNG-CARCINOMA IN MICE

We have found that two chemokines, recombinant gro-alpha and gro-beta, specifically inhibit growth factor-stimulated proliferation of capill ary endothelial cells in a dose-dependent manner, whereas gro-gamma ha s no inhibitory effect. In vivo, gro-beta inhibits blood vessel format ion in the chicken chorioallantoic membrane assay. It is sufficiently potent to effectively suppress basic fibroblast growth factor-induced corneal neovascularization after systemic administration in mice. Furt her, gro-beta significantly inhibits the growth of murine Lewis lung c arcinoma in syngeneic C57Bl6/J and immunodeficient nude mice without t oxicity. In vitro, Lewis lung carcinoma cells are completely insensiti ve to recombinant gro-beta at high concentrations that significantly i nhibit endothelial cell proliferation This finding supports the conclu sion that gro-beta inhibits Lewis lung tumor growth by suppression of tumor-induced neovascularization.