Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels

PC Brooks, AMP Montgomery, M Rosenfeld… - Cell, 1994 - cell.com
PC Brooks, AMP Montgomery, M Rosenfeld, RA Reisfeld, T Hu, G Klier, DA Cheresh
Cell, 1994cell.com
A single intravascular injection of a cyclic peptide or monoclonal antibody antagonist of
integrin ccVps disrupts ongoing angiogenesis on the chick chorioallantoic membrane
(CAM). This leads to the rapid regression of histologically distinct human tumors
transplanted onto the CAM. Induction of angiogenesis by a tumor or cytokine promotes
vascular cell entry into the cell cycle and expression of integrin cc&. After angiogenesis is
initiated, antagonists of this integrin induce apoptosis of the proliferative angiogenic vascular …
Summary
A single intravascular injection of a cyclic peptide or monoclonal antibody antagonist of integrin ccVps disrupts ongoing angiogenesis on the chick chorioallantoic membrane (CAM). This leads to the rapid regression of histologically distinct human tumors transplanted onto the CAM. Induction of angiogenesis by a tumor or cytokine promotes vascular cell entry into the cell cycle and expression of integrin cc&. After angiogenesis is initiated, antagonists of this integrin induce apoptosis of the proliferative angiogenic vascular cells, leaving preexisting quiescent blood vessels unaffected. We demonstrate therefore that ligation of integrin a& is required for the survival and maturation of newly forming blood vessels, an event essential for the proliferation of tumors.
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