Transforming growth factor beta-treated normal 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. Höfler, I. Wehrle, and G. Bauer, Int. J. Cancer, 54: 125-130, 1993). Coculture of normal fibroblasts with transformed cells, either resistant to G 418 or expressing Mx antigen detectable by specific immunofluorescence, 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 able to eliminate transformed cells by induction of apoptosis. Sensitivity against TGF-beta-induced elimination seems to be a general feature of in vitro-transformed cell lines. TGF-beta-induced elimination of transformed fibroblasts by their untransformed counterparts is proposed as a potential potent control point in carcinogenesis, which may lead to the suppression of transformed cells.