Interaction of endostatin with integrins implicated in angiogenesis

Endostatin, a fragment of collagen XVIII, is a potent antagonist of angioge nesis and inhibitor of tumor growth in mouse models. At present, the mechan ism of action of endostatin is unknown. We show here that recombinantly pro duced human endostatin interacts with alpha (5)- and alpha (v)-integrins on the surface of human endothelial cells. We further demonstrate that the en dostatin-integrin interaction is of functional significance in vitro, as we found that immobilized endostatin supports endothelial cell survival and m igration in an integrin-dependent manner. Soluble endostatin in turn inhibi ts integrin-dependent endothelial cell functions, such as cell migration. T aken together, these results implicate integrins as potential targets for e ndostatin function and support the importance of integrins in endothelial c ell biology and angiogenesis.