Integrin alpha 2 beta 1 Is the Required Receptor for Endorepellin Angiostatic Activity

Endorepellin, the C-terminal module of perlecan, has angiostatic activity. Here we provide definitive genetic and biochemical evidence that the functional endorepellin receptor is the alpha 2 beta 1 integrin. Notably, the specific endorepellin binding to the receptor was cation-independent and was m...

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Bibliographic Details
Published in:The Journal of biological chemistry 2008-01, Vol.283 (4), p.2335-2343
Main Authors: Woodall, Benjamin P, Nystroem, Alexander, Iozzo, Rex A, Eble, Johannes A, Niland, Stephan, Krieg, Thomas, Eckes, Beate, Pozzi, Ambra, Iozzo, Renato V
Format: Article
Language:English
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Summary:Endorepellin, the C-terminal module of perlecan, has angiostatic activity. Here we provide definitive genetic and biochemical evidence that the functional endorepellin receptor is the alpha 2 beta 1 integrin. Notably, the specific endorepellin binding to the receptor was cation-independent and was mediated by the alpha 2I domain. We show that the anti-angiogenic effects of endorepellin cannot occur in the absence of alpha 2 beta 1. Microvascular endothelial cells from alpha 2 beta 1 super(-/-) mice, but not those isolated from either wild-type or alpha 1 beta 1 super(-/-) mice, did not respond to endorepellin. Moreover, syngeneic Lewis lung carcinoma xenografts in alpha 2 beta 1 super(-/-) mice failed to respond to systemic delivery of endorepellin. In contrast, endorepellin inhibited tumor growth and angiogenesis in the wild-type mice expressing integrin alpha 2 beta 1. We conclude that the angiostatic effects of endorepellin in vivo are mediated by a specific interaction of endorepellin with the alpha 2 beta 1 integrin receptor.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M708364200