Transforming growth factor-beta: possible roles in carcinogenesis

TGF-beta is the prototype of a large family of multifunctional regulatory proteins. The principal sources of the peptide, platelets and bone, suggest that it plays a role in healing and remodeling processes. In vitro, TGF-beta is chemotactic for monocytes and fibroblasts and can greatly enhance accumulation of extracellular matrix components by fibroblasts. Its ability to stimulate the formation of granulation tissue locally and the demonstration of specific time- and tissue-dependent expression in embryogenesis suggest that similar mechanisms are operative in vivo. By analogy to its effects in wound healing and embryogenesis, it is proposed that TGF-beta, secreted by tumour cells, can augment tumour growth indirectly by effects on the stromal elements. These effects include suppression of the immune response, and enhancement of both angiogenesis and formation of connective tissue. Many tumour cells have escaped from direct growth inhibitory effects of TGF-beta by a variety of mechanisms including inability to activate the latent form of the peptide, loss of cellular receptors for TGF-beta, and loss of functional intracellular signal transduction pathways.