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Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 March 2001, Vol. 97, No. 6, pp. 1679-1684 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Monoclonal antibodies directed to different regions of vascular endothelial cadherin extracellular domain affect adhesion and clustering of the protein and modulate endothelial permeability Monica Corada, Fang Liao, Maria Lindgren, Maria Grazia Lampugnani, Ferruccio Breviario, Ronald Frank, William A. Muller, Daniel J. Hicklin, Peter Bohlen, and Elisabetta Dejana From the Istituto di Ricerche Farmacologiche Mario Negri and Istituto FIRC di Oncologia Molecolare, Milano, Italy; Universita' degli Studi dell' Insubria, Dipartimento di Scienze Cliniche e Biologiche, Facoltà di Medicina e Chirurgia, Varese, Italy; Department of Immunology, ImClone Systems Incorporated, New York, NY; Department of Neurochemistry and Neurotoxicology, Stockholm University, Sweden; AG Molecular Recognition, GBF, Braunschweig, Germany; and Department of Pathology, Weill Medical College of Cornell University, New York, NY. Vascular endothelial cadherin (VE-cadherin) is an endothelial cell-specific cadherin that plays an important role in the control of vascular organization. Blocking VE-cadherin antibodies strongly inhibit angiogenesis, and inactivation of VE-cadherin gene causes embryonic lethality due to a lack of correct organization and remodeling of the vasculature. Hence, inhibitors of VE-cadherin adhesive properties may constitute a tool to prevent tumor neovascularization. In this paper, we tested different monoclonal antibodies (mAbs) directed to human VE-cadherin ectodomain for their functional activity. Three mAbs (Cad 5, BV6, BV9) were able to increase paracellular permeability, inhibit VE-cadherin reorganization, and block angiogenesis in vitro. These mAbs could also induce endothelial cell apoptosis in vitro. Two additional mAbs, TEA 1.31 and Hec 1.2, had an intermediate or undetectable activity, respectively, in these assays. Epitope mapping studies show that BV6, BV9, TEA 1.31, and Hec 1.2 bound to a recombinant fragment spanning the extracellular juxtamembrane domains EC3 through EC4. In contrast, Cad 5 bound to the aminoterminal domain EC1. By peptide scanning analysis and competition experiments, we defined the sequences TIDLRY located on EC3 and KVFRVDAETGDVFAI on EC1 as the binding domain of BV6 and Cad 5, respectively. Overall, these results support the concept that VE-cadherin plays a relevant role on human endothelial cell properties. Antibodies directed to the extracellular domains EC1 but also EC3-EC4 affect VE-cadherin adhesion and clustering and alter endothelial cell permeability, apoptosis, and vascular structure formation. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Regan-Klapisz, V. Krouwer, M. Langelaar-Makkinje, L. Nallan, M. Gelb, H. Gerritsen, A. J. Verkleij, and J. A. Post Golgi-associated cPLA2{alpha} Regulates Endothelial Cell-Cell Junction Integrity by Controlling the Trafficking of Transmembrane Junction Proteins Mol. Biol. Cell, October 1, 2009; 20(19): 4225 - 4234. [Abstract] [Full Text] [PDF] A. B. Salter, S. K. Meadows, G. G. Muramoto, H. Himburg, P. Doan, P. Daher, L. Russell, B. Chen, N. J. Chao, and J. P. 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