Clonal analysis of the effect of TGF-beta on the apoptosis-inducing activity of normal cells.

We have recently described induction of apoptosis in transformed fibroblasts by transforming growth factor type beta (TGF-beta)-treated normal fibroblasts, which leads to the specific elimination of transformed cells. Here we investigate whether the ability to eliminate transformed cells is the property of a specialized subpopulation of normal fibroblasts or whether all cells within the population are able to respond to exogenous TGF-beta by induction of elimination of transformed cells. Clonal analysis of the eliminative capacity of normal fibroblasts showed that all cells are able to induce elimination after addition of optimal concentrations of exogenous TGF-beta. In the absence of exogenously added TGF-beta, a minority of clones exhibited complete eliminative activity. Neither the ability nor the inability to perform elimination in the absence of exogenous TGF-beta was a stable characteristic of the respective cell clones. The number of cell clones with the ability to respond to suboptimal concentrations of TGF-beta increased with the passage number of the normal cells, whereas the number of clones inducing apoptosis in the absence of exogenous TGF-beta remained constant.