[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
TABLE OF CONTENTS
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.