Details

Autor(en) / Beteiligte

• Woodall, Benjamin P
• Nystroem, Alexander
• Iozzo, Rex A
• Eble, Johannes A
• Niland, Stephan
• Krieg, Thomas
• Eckes, Beate
• Pozzi, Ambra
• Iozzo, Renato V

Titel

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

Ist Teil von

• The Journal of biological chemistry, 2008-01, Vol.283 (4), p.2335-2343

Erscheinungsjahr

2008

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.