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 antibody antagonist of integrin alpha v beta 3 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 alpha v beta 3. 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 alpha v beta 3 is required for the survival and maturation of newly forming blood vessels, an event essential for the proliferation of tumors.
Brooks
P C
PC
Department of Immunology, Scripps Research Institute, La Jolla, California 92037.
Montgomery
A M
AM
Rosenfeld
M
M
Reisfeld
R A
RA
Hu
T
T
Klier
G
G
Cheresh
D A
DA
D000482:Allantois / Q000098:blood supply; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001808:Blood Vessels / Q000166:cytology; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000276:immunology*; D016024:Receptors, Cytoadhesin / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D019030:Receptors, Vitronectin; D014407:Tumor Cells, Cultured
D016023:Integrins; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin