FGF-2 AND FGF-1 EXPRESSED IN RAT BLADDER-CARCINOMA CELLS HAVE SIMILARANGIOGENIC POTENTIAL BUT DIFFERENT TUMORIGENIC PROPERTIES IN-VIVO

The comparative biological properties of NET-II cells, a rat bladder c arcinoma cell line constitutively expressing FGF-1 and FGF-2 were anal ysed in nude mice, FGF-1 is not secreted by the transfected cells unle ss the cDNA contains a signal sequence; conversely, NET-II cells trans fected with FGF-2 coding sequence produce and secrete the factor in a biologically active form, Bovine brain capillary endothelial cells are stimulated to proliferate upon addition of medium conditioned by the FGF-2-producing cells and this activity can be abrogated by the additi on of anti-FGF-2 blocking antibodies, In addition, the FGF-2-containin g medium, which cannot stimulate NET-II cells due to absence of approp riate receptors, is able to induce scattering of NET-II cells expressi ng the FGFR1, It has been reported previously that FGF-1-producing cel ls are highly tumorigenic in nude mice and induce carcinoma with a per iod of latency reduced from 6 to 5 weeks when compared to parental NET -II cells, In contrast, NET-II cells producing FGF-2 are no more tumor igenic than parental cells, indicating are no more tumorigenic than pa rental cells, indicating that FGF-1 and FGF-2 have different oncogenic properties in carcinoma, FGF-1 and FGF-2 are potent antiogenic factor s that trigger the host endothelial cells, VEGF, another potent angiog en was found to be expressed in small amounts by NET-II cells and to b e expressed in reduced amount in the FGF-producing cells, In the NET-I I system in vivo FGF-1 and FGF-2 are highly and comparatively angiogen ic in the resultant carcinoma and this occurs in the absence of produc tion of significant amounts of VEGF by the carcinoma cells, Taken toge ther, our results indicate that activated angiogenesis is not sufficie nt for rapid tumor expansion, FGF-1 behaves as a tumorigenic factor in the NET-II bladder carcinoma cell model, whereas expression and secre tion of large amounts of FGF-2 are not sufficient for increasing tumor growth.