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Antibody against junctional adhesion molecule-C inhibits angiogenesis and tumor growth

Hodivala-Dilke, K. M.
Published in Cancer Research. 2005, vol. 65, no. 13, p. 5703-5710
Abstract 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.
Keywords Angiogenesis Inhibitors/ pharmacology/toxicityAnimalsAntibodies, Monoclonal/immunology/ pharmacology/toxicityApoptosis/drug effectsCarcinoma, Lewis Lung/ blood supply/pathology/ therapyCell Adhesion Molecules/ antagonists &inhibitors/biosynthesis/immunology/metabolismCell Growth Processes/drug effectsEndothelial Cells/cytology/drug effects/metabolismFemaleHumansImmunoglobulins/biosynthesis/immunology/metabolismMembrane Proteins/ antagonists & inhibitors/biosynthesis/immunology/metabolismMiceMice, Inbred C57BLNeovascularization, Pathologic/drug therapy/immunology/pathologyNeovascularization, Physiologic/drug effects/immunologyRetinal Vessels/cytologyVascular Endothelial Growth Factor A/metabolism
PMID: 15994945
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LAMAGNA, Chrystelle et al. Antibody against junctional adhesion molecule-C inhibits angiogenesis and tumor growth. In: Cancer research, 2005, vol. 65, n° 13, p. 5703-5710. doi: 10.1158/0008-5472.CAN-04-4012

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Deposited on : 2010-08-27

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