TRANSFORMING GROWTH FACTOR-BETA-TREATED FIBROBLASTS ELIMINATE TRANSFORMED FIBROBLASTS BY INDUCTION OF APOPTOSIS

Transforming growth factor beta (TGF-beta) induces normal fibroblasts to perform an inhibitory effect directed against transformed cells (P. Hofler, I. Wehrle, and G. Bauer, Int. J. Cancer, 54: 125-130, 1993). Coculture of normal fibroblasts with transformed cells, either resista nt to G 418 or expressing Mx antigen detectable by specific immunofluo rescence, allowed discrimination between three theoretical mechanisms of inhibition: irreversible inhibition of proliferation; reversion to the nontransformed phenotype; or elimination of transformed cells. Our data demonstrate that normal fibroblasts treated with TGF-beta are ab le to eliminate transformed cells by induction of apoptosis. Sensitivi ty against TGF-beta-induced elimination seems to be a general feature of in vitro-transformed cell lines. TGF-beta-induced elimination of tr ansformed fibroblasts by their untransformed counterparts is proposed as a potential potent control point in carcinogenesis, which may lead to the suppression of transformed cells.