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

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.

• Authors: Chrystelle Lamagna, Kairbaan M Hodivala-Dilke, Beat A Imhof, Michel Aurrand-Lions
• Journal: Cancer research (Cancer Res) Vol. 65 Issue 13 Pg. 5703-10 (Jul 01 2005) ISSN: 0008-5472 [Print] United States
• PMID: 15994945 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Antibodies, Monoclonal
• Cell Adhesion Molecules
• Immunoglobulins
• JAM3 protein, human
• Membrane Proteins
• Vascular Endothelial Growth Factor A

Topics

• Angiogenesis Inhibitors (pharmacology, toxicity)
• Animals
• Antibodies, Monoclonal (immunology, pharmacology, toxicity)
• Apoptosis (drug effects)
• Carcinoma, Lewis Lung (blood supply, pathology, therapy)
• Cell Adhesion Molecules (antagonists & inhibitors, biosynthesis, immunology, metabolism)
• Cell Growth Processes (drug effects)
• Endothelial Cells (cytology, drug effects, metabolism)
• Female
• Humans
• Immunoglobulins (biosynthesis, immunology, metabolism)
• Membrane Proteins (antagonists & inhibitors, biosynthesis, immunology, metabolism)
• Mice
• Mice, Inbred C57BL
• Neovascularization, Pathologic (drug therapy, immunology, pathology)
• Neovascularization, Physiologic (drug effects, immunology)
• Retinal Vessels (cytology)
• Vascular Endothelial Growth Factor A (metabolism)