Interaction of endostatin with integrins implicated in angiogenesis

Endostatin, a fragment of collagen XVIII, is a potent antagonist of angiogenesis and inhibitor of tumor growth in mouse models. At present, the mechanism of action of endostatin is unknown. We show here that recombinantly produced human endostatin interacts with α 5 - and α v -integrins on the surfa...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2001-01, Vol.98 (3), p.1024-1029
Main Authors: Rehn, Marko, Veikkola, Tanja, Kukk-Valdre, Eola, Nakamura, Hitoshi, Ilmonen, Maritta, Lombardo, Christian R., Pihlajaniemi, Taina, Alitalo, Kari, Vuori, Kristiina
Format: Article
Language:English
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Summary:Endostatin, a fragment of collagen XVIII, is a potent antagonist of angiogenesis and inhibitor of tumor growth in mouse models. At present, the mechanism of action of endostatin is unknown. We show here that recombinantly produced human endostatin interacts with α 5 - and α v -integrins on the surface of human endothelial cells. We further demonstrate that the endostatin–integrin interaction is of functional significance in vitro , as we found that immobilized endostatin supports endothelial cell survival and migration in an integrin-dependent manner. Soluble endostatin in turn inhibits integrin-dependent endothelial cell functions, such as cell migration. Taken together, these results implicate integrins as potential targets for endostatin function and support the importance of integrins in endothelial cell biology and angiogenesis.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.98.3.1024