Monoclonal antibody to vascular endothelial-cadherin is a potent inhibitor of angiogenesis, tumor growth, and metastasis.
Vascular endothelial-cadherin (VE-cad) is an endothelial cell-specific adhesion molecule that is crucial for proper assembly of vascular tubes. Here we show that a monoclonal antibody (BV13) directed to the extracellular region of VE-cad inhibits formation of adherens junctions and capillary-like structures by endothelial cells and blocks angiogenesis in the mouse cornea and in Matrigel plugs in vivo. Systemic administration of BV13 markedly decreases the growth of s.c. Lewis lung or human A431 epidermoid tumors and strongly suppresses the growth of Lewis lung metastases. These data demonstrate that VE-cad is essential for postnatal angiogenesis and thus validate VE-cad as a novel target for antiangiogenesis agents.
Liao
F
F
Department of Immunology, ImClone Systems Incorporated, New York, New York 10014, USA.
Li
Y
Y
O'Connor
W
W
Zanetta
L
L
Bassi
R
R
Santiago
A
A
Overholser
J
J
Hooper
A
A
Mignatti
P
P
Dejana
E
E
Hicklin
D J
DJ
Bohlen
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD; D015820:Cadherins / Q000276:immunology*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D003315:Cornea / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007797:Laminin / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D000099152:Cadherin 5
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015820:Cadherins; D003094:Collagen; D004338:Drug Combinations; D007074:Immunoglobulin G; D007797:Laminin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018809:Proliferating Cell Nuclear Antigen; D011509:Proteoglycans; D000099152:Cadherin 5; C059485:matrigel