The transforming growth factor-beta signaling pathway in tumorigenesis.

Transforming growth factor-beta is believed to play a dual role in carcinogenesis. Through its ability to inhibit cellular proliferation it suppresses tumor development in its early stages, but in the course of tumor progression malignant cells often acquire resistance to growth inhibition by transforming growth factor-beta and themselves secrete large amounts of this cytokine. Transforming growth factor-beta furthers malignant progression in two ways: for one, it acts on nontransformed cells present in the tumor mass to 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, albeit at reduced levels, to be present in the tumor cells themselves.