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Junctional adhesion molecule B interferes with angiogenic VEGF/VEGFR2 signaling

Meguenani, Mehdi and Miljkovic-Licina, Marijana and Fagiani, Ernesta and Ropraz, Patricia and Hammel, Philippe and Aurrand-Lions, Michel and Adams, Ralf H. and Christofori, Gerhard and Imhof, Beat A. and Garrido-Urbani, Sarah. (2015) Junctional adhesion molecule B interferes with angiogenic VEGF/VEGFR2 signaling. The FASEB Journal, Vol. 29, H. 8. pp. 3411-3425.

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Official URL: http://edoc.unibas.ch/dok/A6428636

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Abstract

De novo formation of blood vessels is a pivotal mechanism during cancer development. During the past few years, antiangiogenic drugs have been developed to target tumor vasculature. However, because of limitations and adverse effects observed with current therapies, there is a strong need for alternative antiangiogenic strategies. Using specific anti-junctional adhesion molecule (JAM)-B antibodies and Jam-b-deficient mice, we studied the role in antiangiogenesis of JAM-B. We found that antibodies against murine JAM-B, an endothelium-specific adhesion molecule, inhibited microvessel outgrowth from ex vivo aortic rings and in vitro endothelial network formation. In addition, anti-JAM-B antibodies blocked VEGF signaling, an essential pathway for angiogenesis. Moreover, increased aortic ring branching was observed in aortas isolated from Jam-b-deficient animals, suggesting that JAM-B negatively regulates proangiogenic pathways. In mice, JAM-B expression was detected in de novo-formed blood vessels of tumors, but anti-JAM-B antibodies unexpectedly did not reduce tumor growth. Accordingly, JAM-B deficiency in vivo had no impact on blood vessel formation, suggesting that targeting JAM-B in vivo may be offset by other proangiogenic mechanisms. In conclusion, despite the promising effects observed in vitro, targeting JAM-B during tumor progression seems to be inefficient as a stand-alone antiangiogenesis therapy.-Meguenani, M., Miljkovic-Licina, M., Fagiani, E., Ropraz, P., Hammel, P., Aurrand-Lions, M., Adams, R. H., Christofori, G., Imhof, B. A., Garrido-Urbani, S. Junctional adhesion molecule B interferes with angiogenic VEGF/VEGFR2 signaling.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Tumor Biology (Christofori)
UniBasel Contributors:Christofori, Gerhard M.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:FASEB
ISSN:0892-6638
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:02 Oct 2015 10:01
Deposited On:02 Oct 2015 10:01

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