Details

Autor(en) / Beteiligte

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

Titel

Integrin α2β1 Is the Required Receptor for Endorepellin Angiostatic Activity

Ist Teil von

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

Ort / Verlag

Elsevier Inc

Link zum Volltext

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 α2β1 integrin. Notably, the specific endorepellin binding to the receptor was cation-independent and was mediated by the α2I domain. We show that the anti-angiogenic effects of endorepellin cannot occur in the absence of α2β1. Microvascular endothelial cells from α2β1-/- mice, but not those isolated from either wild-type or α1β1-/- mice, did not respond to endorepellin. Moreover, syngeneic Lewis lung carcinoma xenografts in α2β1-/- mice failed to respond to systemic delivery of endorepellin. In contrast, endorepellin inhibited tumor growth and angiogenesis in the wild-type mice expressing integrin α2β1. We conclude that the angiostatic effects of endorepellin in vivo are mediated by a specific interaction of endorepellin with the α2β1 integrin receptor.