TGF-ß, Bone Morphogenetic Protein, and Activin Signaling and the Tumor Microenvironment.

ABSTRACT

The cellular and noncellular components surrounding the tumor cells influence many aspects of tumor progression. Transforming growth factor ß (TGF-ß), bone morphogenetic proteins (BMPs), and activins have been shown to regulate the phenotype and functions of the microenvironment and are attractive targets to attenuate protumorigenic microenvironmental changes. Given the pleiotropic nature of the cytokines involved, a full understanding of their effects on numerous cell types in many contexts is necessary for proper clinical intervention. In this review, we will explore the various effects of TGF-ß, BMP, and activin signaling on stromal phenotypes known to associate with cancer progression. We will summarize these findings in the context of their tumor suppressive or promoting effects, as well as the molecular changes that these cytokines induce to influence stromal phenotypes.