TGF-beta isoforms and fibroblast growth factor exhibit analogous indirect antioncogenic activity through triggering of intercellular induction of apoptosis.

TGF-beta-1 has recently been shown to trigger nontransformed effector cells to induce apoptosis specifically in transformed cells. This intercellular induction of apoptosis has been discussed as a potential control step in oncogenesis. Here we show that triggering of intercellular induction of apoptosis is not a non-specific growth factor effect, but is restricted to the TGF-beta and FGF family of growth factors. Within the TGF-beta family, all isoforms triggered the intercellular induction of apoptosis with the same efficiency. This finding illustrates that these effects observed have been conserved throughout evolution, which thus points to their potential biological significance. The parallel action of TGF-beta and FGF in the intercellular induction of apoptosis correlates with the role of both families of factors in the establishment and maintenance of the transformed state. Autocrine loops of either growth factor seem to be recognized by the surrounding nontransformed cells and to evoke an apoptosis- inducing effect which thus prevents the survival and outgrowth of potential tumor cells.