Role of transforming growth factor beta in cancer

Abstract

Transforming growth factor beta (TGF‐β) is an effective and ubiquitous mediator of cell growth. The significance of this cytokine in cancer susceptibility, cancer development and progression has become apparent over the past few years. TGF‐β plays various roles in the process of malignant progression. It is a potent inhibitor of normal stromal, hematopoietic, and epithelial cell growth. However, at some point during cancer development the majority of transformed cells become either partly or completely resistant to TGF‐β growth inhibition. There is growing evidence that in the later stages of cancer development TGF‐β is actively secreted by tumor cells and not merely acts as a bystander but rather contributes to cell growth, invasion, and metastasis and decreases host‐tumor immune responses. Subtle alteration of TGF‐β signaling may also contribute to the development of cancer. These various effects are tissue and tumor dependent. Identifying and understanding TGF‐β signaling pathway abnormalities in various malignancies is a promising avenue of study that may yield new modalities to both prevent and treat cancer. The nature, prevalence, and significance of TGF‐β signaling pathway alterations in various forms of human cancer as well as potential preventive and therapeutic interventions are discussed in this review. J. Cell. Physiol. 186:153–168, 2001.