Inflammation and Beyond: Complex Roles for TGF- β in the Tumor Microenvironment
Pp. 123-154 (32)
Dror Luger and Lalage M. Wakefield
TGF-βs are pleiotropic regulatory proteins that are often highly overexpressed in the
microenvironment of advanced tumors. Since nearly all cell types respond to TGF-β, TGF-βs are wellpositioned
to integrate cellular responses in the parenchymal and stromal compartments of normal
tissues and of tumors, and to mediate cross-talk between the two. Pre-clinical studies have uncovered
complex roles for TGF-βs in tumorigenesis, with tumor suppressive and tumor promoting effects on
both compartments. In this review, we discuss the biological activities of TGF-β that underlie these
effects and address some of the mechanisms that determine which type of effect dominates at different
stages of the tumorigenic process. Finally, we consider the prospects for therapeutic targeting of TGF-β
in cancer, as a way to simultaneously normalize both the microenvironmental and parenchymal
compartments of the tumor, and thus prevent or reverse tumor progression.
TGF-beta, immunosuppression, inflammation, smad, tumor suppression, metastasis, cancer therapy.
Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda MD 20892, USA