SEARCH:   Advanced

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Corada, M. Articles by Dejana, E. Search for Related Content PubMed PubMed Citation Articles by Corada, M. Articles by Dejana, E. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2002, Vol. 100, No. 3, pp. 905-911 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY A monoclonal antibody to vascular endothelial-cadherin inhibits tumor angiogenesis without side effects on endothelial permeability Monica Corada, Lucia Zanetta, Fabrizio Orsenigo, Ferruccio Breviario, Maria Grazia Lampugnani, Sergio Bernasconi, Fang Liao, Daniel J. Hicklin, Peter Bohlen, and Elisabetta Dejana From the FIRC Institute of Molecular Oncology, Milan, Italy; Mario Negri Institute for Pharmacological Research, Milan, Italy; Universitá degli Studi dell'Insubria, Dipartimento di Scienze Cliniche e Biologiche, Facoltá di Medicina e Chirurgia, Varese, Italy; Department of Immunology, ImClone Systems Incorporated, New York, NY. Vascular endothelial cadherin (VE-cadherin) is an endothelial-specific, trans-membrane protein that promotes homophilic cell adhesion. Inhibition of VE-cadherin by the blocking monoclonal antibody (mAb) BV13 inhibited angiogenesis and tumor growth in vivo. However, this effect was accompanied by a marked increase in lung and heart permeability. In the present paper, we characterize a different VE-cadherin mAb (BV14) that is able to inhibit angiogenesis without affecting vascular permeability. In vitro studies show that BV14, in contrast to BV13, did not increase paracellular permeability of endothelial monolayers and did not disrupt VE-cadherin clusters at junctions. However, both antibodies could inhibit formation of vascularlike structures in collagen gels and increase migration of endothelial cells into wounded areas. In vivo, BV14 and BV13 were equally active in inhibiting angiogenesis in the mouse cornea and in reducing the growth of hemangioma and C6 glioma. In contrast to BV13, BV14 did not change vascular permeability in all the organs tested and at any dose used. BV14 and BV13 bind to VE-cadherin extracellular repeats EC4 and EC1, respectively. We propose that, in resting vessels, where junctions are stable and well-structured, antibody binding to EC1 but not EC4 disrupts their organization and increases permeability. In contrast, in growing vessels, where endothelial cells are migrating and junctions are weaker, antibody binding to EC4 may be sufficient to disrupt cell-to-cell adhesion and inhibit assembly of new vascular structures. © 2002 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: D. Navaratna, J. Maestas, P. G. McGuire, and A. Das Suppression of Retinal Neovascularization With an Antagonist to Vascular Endothelial Cadherin Arch Ophthalmol, August 1, 2008; 126(8): 1082 - 1088. [Abstract] [Full Text] [PDF] M. Labelle, H. J. Schnittler, D. E. Aust, K. Friedrich, G. Baretton, D. Vestweber, and G. Breier Vascular Endothelial Cadherin Promotes Breast Cancer Progression via Transforming Growth Factor {beta} Signaling Cancer Res., March 1, 2008; 68(5): 1388 - 1397. [Abstract] [Full Text] [PDF] D. Vestweber VE-Cadherin: The Major Endothelial Adhesion Molecule Controlling Cellular Junctions and Blood Vessel Formation Arterioscler Thromb Vasc Biol, February 1, 2008; 28(2): 223 - 232. [Abstract] [Full Text] [PDF] K. Xiao, J. Garner, K. M. Buckley, P. A. Vincent, C. M. Chiasson, E. Dejana, V. Faundez, and A. P. Kowalczyk p120-Catenin Regulates Clathrin-dependent Endocytosis of VE-Cadherin Mol. Biol. Cell, November 1, 2005; 16(11): 5141 - 5151. [Abstract] [Full Text] [PDF] A. Bratt, O. Birot, I. Sinha, N. Veitonmaki, K. Aase, M. Ernkvist, and L. Holmgren Angiomotin Regulates Endothelial Cell-Cell Junctions and Cell Motility J. Biol. Chem., October 14, 2005; 280(41): 34859 - 34869. [Abstract] [Full Text] [PDF] K. Shiraishi, K. Tsuzaka, K. Yoshimoto, C. Kumazawa, K. Nozaki, T. Abe, K. Tsubota, and T. Takeuchi Critical Role of the Fifth Domain of E-Cadherin for Heterophilic Adhesion with {alpha}E{beta}7, But Not for Homophilic Adhesion J. Immunol., July 15, 2005; 175(2): 1014 - 1021. [Abstract] [Full Text] [PDF] J. D. van Buul, E. C. Anthony, M. Fernandez-Borja, K. Burridge, and P. L. Hordijk Proline-rich Tyrosine Kinase 2 (Pyk2) Mediates Vascular Endothelial-Cadherin-based Cell-Cell Adhesion by Regulating {beta}-Catenin Tyrosine Phosphorylation J. Biol. Chem., June 3, 2005; 280(22): 21129 - 21136. [Abstract] [Full Text] [PDF] C. May, J. F. Doody, R. Abdullah, P. Balderes, X. Xu, C. P. Chen, Z. Zhu, L. Shapiro, P. Kussie, D. J. Hicklin, et al. Identification of a transiently exposed VE-cadherin epitope that allows for specific targeting of an antibody to the tumor neovasculature Blood, June 1, 2005; 105(11): 4337 - 4344. [Abstract] [Full Text] [PDF] C. V. Crosby, P. A. Fleming, W. S. Argraves, M. Corada, L. Zanetta, E. Dejana, and C. J. Drake VE-cadherin is not required for the formation of nascent blood vessels but acts to prevent their disassembly Blood, April 1, 2005; 105(7): 2771 - 2776. [Abstract] [Full Text] [PDF] G. S. Nakhuda, R. C. Zimmermann, P. Bohlen, F. Liao, M. V. Sauer, and J. Kitajewski Inhibition of the Vascular Endothelial Cell (VE)-Specific Adhesion Molecule VE-Cadherin Blocks Gonadotropin-Dependent Folliculogenesis and Corpus Luteum Formation and Angiogenesis Endocrinology, March 1, 2005; 146(3): 1053 - 1059. [Abstract] [Full Text] [PDF] N. Lambeng, Y. Wallez, C. Rampon, F. Cand, G. Christe, D. Gulino-Debrac, I. Vilgrain, and P. Huber Vascular Endothelial-Cadherin Tyrosine Phosphorylation in Angiogenic and Quiescent Adult Tissues Circ. Res., February 18, 2005; 96(3): 384 - 391. [Abstract] [Full Text] [PDF] T.-S. Li, H. Ito, M. Hayashi, A. Furutani, M. Matsuzaki, and K. Hamano Cellular expression of integrin-{beta}1 is of critical importance for inducing therapeutic angiogenesis by cell implantation Cardiovasc Res, January 1, 2005; 65(1): 64 - 72. [Abstract] [Full Text] [PDF] B. S. Parker, P. Argani, B. P. Cook, H. Liangfeng, S. D. Chartrand, M. Zhang, S. Saha, A. Bardelli, Y. Jiang, T. B. St. Martin, et al. Alterations in Vascular Gene Expression in Invasive Breast Carcinoma Cancer Res., November 1, 2004; 64(21): 7857 - 7866. [Abstract] [Full Text] [PDF] S. Boitano, Z. Safdar, D. G. Welsh, J. Bhattacharya, and M. Koval Cell-cell interactions in regulating lung function Am J Physiol Lung Cell Mol Physiol, September 1, 2004; 287(3): L455 - L459. [Abstract] [Full Text] [PDF] G. Bazzoni and E. Dejana Endothelial Cell-to-Cell Junctions: Molecular Organization and Role in Vascular Homeostasis Physiol Rev, July 1, 2004; 84(3): 869 - 901. [Abstract] [Full Text] [PDF] M. Iurlaro, F. Demontis, M. Corada, L. Zanetta, C. Drake, M. Gariboldi, S. Peiro, A. Cano, P. Navarro, A. Cattelino, et al. VE-Cadherin Expression and Clustering Maintain Low Levels of Survivin in Endothelial Cells Am. J. Pathol., July 1, 2004; 165(1): 181 - 189. [Abstract] [Full Text] [PDF] P. A. Vincent, K. Xiao, K. M. Buckley, and A. P. Kowalczyk VE-cadherin: adhesion at arm's length Am J Physiol Cell Physiol, May 1, 2004; 286(5): C987 - C997. [Abstract] [Full Text] [PDF] F. Zhang, J. Cheng, N. R. Hackett, G. Lam, K. Shido, R. Pergolizzi, D. K. Jin, R. G. Crystal, and S. Rafii Adenovirus E4 Gene Promotes Selective Endothelial Cell Survival and Angiogenesis via Activation of the Vascular Endothelial-Cadherin/Akt Signaling Pathway J. Biol. Chem., March 19, 2004; 279(12): 11760 - 11766. [Abstract] [Full Text] [PDF] M.-T. Lin, M.-L. Yen, C.-Y. Lin, and M.-L. Kuo Inhibition of Vascular Endothelial Growth Factor-Induced Angiogenesis by Resveratrol through Interruption of Src-Dependent Vascular Endothelial Cadherin Tyrosine Phosphorylation Mol. Pharmacol., November 1, 2003; 64(5): 1029 - 1036. [Abstract] [Full Text] [PDF] A. Cattelino, S. Liebner, R. Gallini, A. Zanetti, G. Balconi, A. Corsi, P. Bianco, H. Wolburg, R. Moore, B. Oreda, et al. The conditional inactivation of the {beta}-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular fragility J. Cell Biol., September 15, 2003; 162(6): 1111 - 1122. [Abstract] [Full Text] [PDF] V. Chhokar and A. L. Tucker Angiogenesis: Basic Mechanisms and Clinical Applications Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2003; 7(3): 253 - 280. [Abstract] [PDF] M. G. Lampugnani, A. Zanetti, M. Corada, T. Takahashi, G. Balconi, F. Breviario, F. Orsenigo, A. Cattelino, R. Kemler, T. O. Daniel, et al. Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, {beta}-catenin, and the phosphatase DEP-1/CD148 J. Cell Biol., May 26, 2003; 161(4): 793 - 804. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020