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Junctional adhesion molecule B interferes with angiogenic VEGF/VEGFR2 signaling

Fagiani, Ernesta
Adams, Ralf H
Christofori, Gerhard
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Published in The FASEB journal. 2015, vol. 29, no. 8, p. 3411-25
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.
Keywords AnimalsCell Adhesion Molecules/metabolismCell Line, TumorFemaleMiceMice, Inbred C57BLNeovascularization, Pathologic/metabolismSignal Transduction/physiologyVascular Endothelial Growth Factor A/metabolismVascular Endothelial Growth Factor Receptor-2/metabolism
PMID: 25911611
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Research group Molécules d'adhésion et processus de migration cellulaire (167)
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MEGUENANI, Mehdi et al. Junctional adhesion molecule B interferes with angiogenic VEGF/VEGFR2 signaling. In: The FASEB journal, 2015, vol. 29, n° 8, p. 3411-25. doi: 10.1096/fj.15-270223 https://archive-ouverte.unige.ch/unige:83913

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Deposited on : 2016-05-27

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