Junctional adhesion molecule B interferes with angiogenic VEGF/VEGFR2 signaling.
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.
*Department of Pathology and Immunology, Medical Faculty, University Medical Center, University of Geneva, Geneva, Switzerland; Department of Biomedicine, Institute of Biochemistry and Genetics, University of Basel, Basel, Switzerland; Unité Mixte de Recherche 1068, Centre de Recherche en Cancérologie de Marseille, Institut National de la Santé et de la Recherche Médicale, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Marseille Université, Marseille, France; Unité Mixte de Recherche 7258, Centre National de la Recherche Scientifique, Marseille, France; Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine, Münster, Münster, Germany; and Faculty of Medicine, University of Münster, Münster, Germany.
Mehdi
M
Meguenani
*Department of Pathology and Immunology, Medical Faculty, University Medical Center, University of Geneva, Geneva, Switzerland; Department of Biomedicine, Institute of Biochemistry and Genetics, University of Basel, Basel, Switzerland; Unité Mixte de Recherche 1068, Centre de Recherche en Cancérologie de Marseille, Institut National de la Santé et de la Recherche Médicale, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Marseille Université, Marseille, France; Unité Mixte de Recherche 7258, Centre National de la Recherche Scientifique, Marseille, France; Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine, Münster, Münster, Germany; and Faculty of Medicine, University of Münster, Münster, Germany.
Marijana
M
Miljkovic-Licina
*Department of Pathology and Immunology, Medical Faculty, University Medical Center, University of Geneva, Geneva, Switzerland; Department of Biomedicine, Institute of Biochemistry and Genetics, University of Basel, Basel, Switzerland; Unité Mixte de Recherche 1068, Centre de Recherche en Cancérologie de Marseille, Institut National de la Santé et de la Recherche Médicale, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Marseille Université, Marseille, France; Unité Mixte de Recherche 7258, Centre National de la Recherche Scientifique, Marseille, France; Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine, Münster, Münster, Germany; and Faculty of Medicine, University of Münster, Münster, Germany.
Ernesta
E
Fagiani
*Department of Pathology and Immunology, Medical Faculty, University Medical Center, University of Geneva, Geneva, Switzerland; Department of Biomedicine, Institute of Biochemistry and Genetics, University of Basel, Basel, Switzerland; Unité Mixte de Recherche 1068, Centre de Recherche en Cancérologie de Marseille, Institut National de la Santé et de la Recherche Médicale, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Marseille Université, Marseille, France; Unité Mixte de Recherche 7258, Centre National de la Recherche Scientifique, Marseille, France; Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine, Münster, Münster, Germany; and Faculty of Medicine, University of Münster, Münster, Germany.
Patricia
P
Ropraz
*Department of Pathology and Immunology, Medical Faculty, University Medical Center, University of Geneva, Geneva, Switzerland; Department of Biomedicine, Institute of Biochemistry and Genetics, University of Basel, Basel, Switzerland; Unité Mixte de Recherche 1068, Centre de Recherche en Cancérologie de Marseille, Institut National de la Santé et de la Recherche Médicale, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Marseille Université, Marseille, France; Unité Mixte de Recherche 7258, Centre National de la Recherche Scientifique, Marseille, France; Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine, Münster, Münster, Germany; and Faculty of Medicine, University of Münster, Münster, Germany.
Philippe
P
Hammel
*Department of Pathology and Immunology, Medical Faculty, University Medical Center, University of Geneva, Geneva, Switzerland; Department of Biomedicine, Institute of Biochemistry and Genetics, University of Basel, Basel, Switzerland; Unité Mixte de Recherche 1068, Centre de Recherche en Cancérologie de Marseille, Institut National de la Santé et de la Recherche Médicale, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Marseille Université, Marseille, France; Unité Mixte de Recherche 7258, Centre National de la Recherche Scientifique, Marseille, France; Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine, Münster, Münster, Germany; and Faculty of Medicine, University of Münster, Münster, Germany.
Michel
M
Aurrand-Lions
*Department of Pathology and Immunology, Medical Faculty, University Medical Center, University of Geneva, Geneva, Switzerland; Department of Biomedicine, Institute of Biochemistry and Genetics, University of Basel, Basel, Switzerland; Unité Mixte de Recherche 1068, Centre de Recherche en Cancérologie de Marseille, Institut National de la Santé et de la Recherche Médicale, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Marseille Université, Marseille, France; Unité Mixte de Recherche 7258, Centre National de la Recherche Scientifique, Marseille, France; Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine, Münster, Münster, Germany; and Faculty of Medicine, University of Münster, Münster, Germany.
Ralf H
RH
Adams
*Department of Pathology and Immunology, Medical Faculty, University Medical Center, University of Geneva, Geneva, Switzerland; Department of Biomedicine, Institute of Biochemistry and Genetics, University of Basel, Basel, Switzerland; Unité Mixte de Recherche 1068, Centre de Recherche en Cancérologie de Marseille, Institut National de la Santé et de la Recherche Médicale, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Marseille Université, Marseille, France; Unité Mixte de Recherche 7258, Centre National de la Recherche Scientifique, Marseille, France; Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine, Münster, Münster, Germany; and Faculty of Medicine, University of Münster, Münster, Germany.
Gerhard
G
Christofori
*Department of Pathology and Immunology, Medical Faculty, University Medical Center, University of Geneva, Geneva, Switzerland; Department of Biomedicine, Institute of Biochemistry and Genetics, University of Basel, Basel, Switzerland; Unité Mixte de Recherche 1068, Centre de Recherche en Cancérologie de Marseille, Institut National de la Santé et de la Recherche Médicale, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Marseille Université, Marseille, France; Unité Mixte de Recherche 7258, Centre National de la Recherche Scientifique, Marseille, France; Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine, Münster, Münster, Germany; and Faculty of Medicine, University of Münster, Münster, Germany sarah.garrido-urbani@unige.ch beat.imhof@unige.ch.
Beat A
BA
Imhof
*Department of Pathology and Immunology, Medical Faculty, University Medical Center, University of Geneva, Geneva, Switzerland; Department of Biomedicine, Institute of Biochemistry and Genetics, University of Basel, Basel, Switzerland; Unité Mixte de Recherche 1068, Centre de Recherche en Cancérologie de Marseille, Institut National de la Santé et de la Recherche Médicale, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Marseille Université, Marseille, France; Unité Mixte de Recherche 7258, Centre National de la Recherche Scientifique, Marseille, France; Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine, Münster, Münster, Germany; and Faculty of Medicine, University of Münster, Münster, Germany sarah.garrido-urbani@unige.ch beat.imhof@unige.ch.
Sarah
S
Garrido-Urbani
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D062765:Junctional Adhesion Molecule B
D015815:Cell Adhesion Molecules; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; C498781:Jam2 protein, mouse; D062765:Junctional Adhesion Molecule B; C467480:vascular endothelial growth factor A, mouse; C000592875:Kdr protein, mouse
aortic ring; endothelial cells; tumor angiogenesis