INTEGRIN ALPHA(V)BETA(3) ANTAGONISTS PROMOTE TUMOR-REGRESSION BY INDUCING APOPTOSIS OF ANGIOGENIC BLOOD-VESSELS

A single intravascular injection of a cyclic peptide or monoclonal ant ibody antagonist of integrin alpha(v) beta(3) disrupts ongoing angioge nesis on the chick chorioallantoic membrane (CAM). This leads to the r apid regression of histologically distinct human tumors transplanted o nto the CAM. Induction of angiogenesis by a tumor or cytokine promotes vascular cell entry into the cell cycle and expression of integrin al pha(v) beta(3). After angiogenesis is initiated, antagonists of this i ntegrin induce apoptosis of the proliferative angiogenic vascular cell s, leaving preexisting quiescent blood vessels unaffected. We demonstr ate therefore that ligation of integrin alpha(v) beta(3) is required f or the survival and maturation of newly forming blood vessels, an even t essential for the proliferation of tumors.