The transforming growth factor-beta signaling pathway in tumorigenesis

Transforming growth factor-beta is believed to play a dual role in carcinog enesis. Through its ability to inhibit cellular proliferation it suppresses tumor development in its early stages, but in the course of tumor progress ion malignant cells often acquire resistance to growth inhibition by transf orming growth factor-beta and themselves secrete large amounts of this cyto kine. Transforming growth factor-beta furthers malignant progression in two ways: for one, it acts on nontransformed cells present in the tumor mass t o suppress antitumor immune responses and to augment angiogenesis. Secondly , it promotes invasion and the formation of metastases in a cell-autonomous manner that requires transforming growth factor-beta signaling activity, a lbeit at reduced levels, to be present in the tumor cells themselves. Curr Opin Oncol 2001, 13:70-77 (C) 2001 Lippincott Williams & Wilkins, Inc.