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 …