Integrins and angiogenesis: A sticky business

From an evolutionary point of view the development of a cardiovascular system allowed vertebrates to nourish the several organs that compose their wider multicellular organism and to Survive. Acquisition of new genes encoding for extracellular matrix (ECM) proteins and their cognate integrin receptors as well as secreted pro- and anti-angiogenic factors proved to be essential for the development of vascular networks in the vertebrate embryo. Postnatal tissue neo-vascularization plays a key role during wound healing and pathological angiogenesis as well. There is now clear evidence that building blood vessels in the embryo and in the adult organism relies upon different endothelial integrins and ECM ligands. A successful vascular development depends on fibronectin and its major receptor alpha 5 beta 1 integrin, but not on alpha v beta 3, alpha v beta 5, and alpha 6 beta 4 integrins that are instead central regulators of postnatal tumor angiogenesis. Here, endothelial alpha v beta 3 elicits anti- or pro-angiogenic signals depending respectively on whether it is occupied by a soluble (e.g. type IV collagen derived tumstatin) or an insoluble (vitronectin) ECM ligand. The laminin-5 receptor alpha 6 beta 4 integrin, expressed only by endothelial cells of mature blood vessels, controls the invasive phase of turner angiogenesis in the adult organism. Finally, regulation of vascular morphogenesis relies upon the fine modulation of integrin activation by chemoattractant and chemorepulsive cues, such as angiogenic growth factors and semaphorin. (c) 2005 Elsevier Inc. All rights reserved.