[HTML][HTML] Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity
PC Brooks, S Silletti, TL von Schalscha, M Friedlander… - Cell, 1998 - cell.com
PC Brooks, S Silletti, TL von Schalscha, M Friedlander, DA Cheresh
Cell, 1998•cell.comAngiogenesis depends on both cell adhesion and proteolytic mechanisms. In fact, matrix
metalloproteinase 2 (MMP-2) and integrin αvβ3 are functionally associated on the surface of
angiogenic blood vessels. A fragment of MMP-2, which comprises the C-terminal hemopexin-
like domain, termed PEX, prevents this enzyme binding to αvβ3 and blocks cell surface
collagenolytic activity. PEX blocks MMP-2 activity on the chick chorioallantoic membrane
where it disrupts angiogenesis and tumor growth. Importantly, a naturally occurring form of …
metalloproteinase 2 (MMP-2) and integrin αvβ3 are functionally associated on the surface of
angiogenic blood vessels. A fragment of MMP-2, which comprises the C-terminal hemopexin-
like domain, termed PEX, prevents this enzyme binding to αvβ3 and blocks cell surface
collagenolytic activity. PEX blocks MMP-2 activity on the chick chorioallantoic membrane
where it disrupts angiogenesis and tumor growth. Importantly, a naturally occurring form of …
Abstract
Angiogenesis depends on both cell adhesion and proteolytic mechanisms. In fact, matrix metalloproteinase 2 (MMP-2) and integrin αvβ3 are functionally associated on the surface of angiogenic blood vessels. A fragment of MMP-2, which comprises the C-terminal hemopexin-like domain, termed PEX, prevents this enzyme binding to αvβ3 and blocks cell surface collagenolytic activity. PEX blocks MMP-2 activity on the chick chorioallantoic membrane where it disrupts angiogenesis and tumor growth. Importantly, a naturally occurring form of PEX can be detected in vivo in conjunction with αvβ3 expression in tumors and during developmental retinal neovascularization. Levels of PEX in these vascularized tissues suggest that it interacts with endothelial cell αvβ3 where it serves as a natural inhibitor of MMP-2 activity, thereby regulating the invasive behavior of new blood vessels.
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