Suppression of tumor angiogenesis through the inhibition of integrin function and signaling in endothelial cells: which side to target?

Tumor angiogenesis is an essential step in tumor progression and metastasis formation. Suppression of tumor angiogenesis results in the inhibition of tumor growth. Recent evidence indicates that vascular integrins, in particular f V g 3, are important regulators of angiogenesis, including tumor angiogenesis. Integrin f V g 3 antagonists, such as blocking antibodies or peptides, suppress tumor angiogenesis and tumor progression in many preclinical tumor models. The potential therapeutic efficacy of extracellular integrin antagonists in human cancer is currently being tested in clinical trials. Selective disruption of the tumor vasculature by high doses of tumor necrosis factor (TNF) and interferon gamma (IFN- n ), and the antiangiogenic activity of nonsteroidal anti-inflammatory drugs are associated with the suppression of integrin f V g 3 function and signaling in endothelial cells. Furthermore, expression of isolated integrin cytoplasmic domains disrupts integrin-dependent adh...