Three distinct roles for TGF-beta during intercellular induction of apoptosis: A review

During intercellular induction of apoptosis, transformed fibroblasts are el iminated through the action of neighbouring nontransformed cells. TGF-beta thereby plays three distinct and central roles a) TGF-beta released by tran sformed cells or added exogenously to the assay system triggers nontransfor med cells to release a shortlived apoptosis inducing factor, which is speci fically directed against transformed cells. b) TGF-beta is involved in the maintenance of the transformed state, which is required for expression of s ensitivity for intercellular induction of apoptosis, c) TGF-beta further se nsitizes transformed cells through downmodulation of their endogenous survi val factors, which control a constitutively expressed apoptosis machinery. These data demonstrate that TGF-beta which is utilized by transformed fibro blasts for the maintenance of their transformed state, causes recognition o f transformed cells by their nontransformed neighbours and triggers and enh ances an apoptosis-inducing response which finally causes elimination of po tential tumor cells.