Tumor-suppressive and promoting function of transforming growth factor beta.

Transforming growth factor beta (TGFbeta) is a multifunctional polypeptide. Its role in carcinogenesis can be either suppressive or promoting depending on tumor developmental stages and cellular context. During the early phase of epithelial tumorigenesis, TGFbeta inhibits primary tumor development and growth by inducing cell cycle arrest and possibly apoptosis. However, in late stages of progression, as tumor cells evade the growth inhibition by TGFbeta due to inactivation of its signaling pathway or aberrant regulation of cell cycle machinery, the role of TGFbeta signaling is often switched from tumor suppression to promotion. TGFbeta can apparently act in tumor stroma as well as tumor cells to inhibit host immune surveillance and stimulate invasion, angiogenesis, and metastasis. Studies have shown that antagonizing TGFbeta activity can inhibit tumor progression, especially metastasis, in certain tumor models. However, the molecular markers that can indicate the feasibility of the use of TGFbeta antagonists as cancer therapeutics remain to be determined.