Antibody against junctional adhesion molecule-C inhibits angiogenesis and tumor growth.
The junctional adhesion molecule-C (JAM-C) was recently described as an adhesion molecule localized at interendothelial contacts and involved in leukocyte transendothelial migration. The protein JAM-C interacts with polarity complex molecules and regulates the activity of the small GTPase Cdc42. The angiogenesis process involves rearrangement of endothelial junctions and implicates modulation of cell polarity. We tested whether JAM-C plays a role in angiogenesis using tumor grafts and hypoxia-induced retinal neovascularization. Treatment with a monoclonal antibody directed against JAM-C reduces tumor growth and infiltration of macrophages into tumors. The antibody decreases angiogenesis in the model of hypoxia-induced retinal neovascularization in vivo and vessel outgrowth from aortic rings in vitro. Importantly, the antibody does not induce pathologic side effects in vivo. These findings show for the first time a role for JAM-C in angiogenesis and define JAM-C as a valuable target for antitumor therapies.
Lamagna
Chrystelle
C
Department of Pathology and Immunology, Centre Médical Universitaire, Geneva, Switzerland.
Hodivala-Dilke
Kairbaan M
KM
Imhof
Beat A
BA
Aurrand-Lions
Michel
M
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D018827:Carcinoma, Lewis Lung / Q000098:blood supply* / Q000473:pathology / Q000628:therapy*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000276:immunology; D012171:Retinal Vessels / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C448000:JAM3 protein, human; D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A