Stromal Modulators of TGF-β in Cancer

Transforming growth factor-beta (TGF-beta) is an intriguing cytokine exhibiting dual activities in malignant disease. It is an important mediator of cancer invasion, metastasis and angiogenesis, on the one hand, while it exhibits anti-tumor functions on the other hand. Elucidating the precise role of TGF-beta in malignant development and progression requires a better understanding of the molecular mechanisms involved in its tumor suppressor to tumor promoter switch. One important aspect of TGF-beta function is its interaction with proteins within the tumor microenvironment. Several stromal proteins have the natural ability to interact and modulate TGF-beta function. Understanding the complex interplay between the TGF-beta signaling network and these stromal proteins may provide greater insight into the development of novel therapeutic strategies that target the TGF-beta axis. The present review highlights our present understanding of how stroma modulates TGF-beta activity in human cancers.