[Frontiers in Bioscience 14, 4848-4861, June 1, 2009]

Transforming growth factor-beta signaling and tumor angiogenesis

Evangelia Pardali, Peter ten Dijke

Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands


1. Abstract
2. Introduction
3. TGF-beta signaling pathways
4. TGF-beta and vascular development
5. BMP and vascular development
6. Role of TGF-beta signaling in maintenance of vascular integrity
7. Tumor Angiogenesis
7.1. TGF-beta and tumor angiogenesis
7.2. Role of Smads in tumor angiogenesis
7.3. Role of Endoglin in tumor angiogenesis
7.4. BMP and tumor angiogenesis
8. Future perspectives
9. Acknowledgments
10. References


Transforming growth factor-beta (TGF-beta) family members are secreted multifunctional cytokines that play pivotal roles in development and disease. The prototypic member of this family, TGF-beta, plays a dual role in carcinogenesis, acting as a tumor suppressor in early stages and as tumor promoter in late stages of tumor progression. Numerous studies support the notion that pathological angiogenesis is one of the hallmarks of cancer. Tumor angiogenesis is regulated by a network of growth factors, including members of the TGF-beta family. TGF-beta acts in a context-dependent manner and can either stimulate or inhibit tumor angiogenesis. In this review, we discuss our current understanding on how TGF-beta family members affect endothelial and smooth muscle cell function and how perturbed TGF-beta signaling may contribute to tumor angiogenesis and tumor progression.