TGF-BETA-INDUCED APOPTOSIS OF TRANSFORMED FIBROBLASTS BY NORMAL FIBROBLASTS - INDEPENDENCE OF CELL-TO-CELL CONTACT AND DEPENDENCE ON REACTIVE OXYGEN SPECIES

We studied the elimination of transformed fibroblasts induced by TGF-b eta-treated normal fibroblasts. Kinetic experiments revealed two steps : First, the elimination process is induced in the normal cells by TGF -beta and later, the apoptosis of transformed cells is mediated by a s hort-lived effector different from TGF-beta and TNF. The killing of th e transformed cells is directly observable as a cytopathic effect. It does not depend on cell-to-cell contact between normal and transformed cells. Reactive oxygen species (ROS) play an important role in the el imination process but are not the apoptosis-inducing signal transmitte d from TGF-beta-treated normal cells.