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Prepublished online as a Blood First Edition Paper on February 27, 2003; DOI 10.1182/blood-2002-04-1004. This Article Full Text (PDF) All Versions of this Article: 2002-04-1004v1 102/1/184    most recent Alert me when this article is cited Alert me if a correction is posted 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 Yan, X. Articles by Bader, B. L Search for Related Content PubMed PubMed Citation Articles by Yan, X. Articles by Bader, B. L Social Bookmarking                   What's this? Submitted June 26, 2002 Accepted February 12, 2003 A novel anti-CD146 monoclonal antibody, AA98, inhibits angiogenesis and tumor growth Xiyun Yan*, Yun Lin, Dongling Yang, Yi Shen, Mei Yuan, Zhiqiang Zhang, Peiyu Li, Hongtian Xia, Li Li, Dandan Luo, Qin Liu, Karlheinz Mann, and Bernhard L Bader Center of Molecular Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China Department of Tumor Biology, General Hospital of PLA, Beijing, China Department of Protein Chemistry, Max-Planck-Institute for Biochemistry, Munich, Germany Department of Molecular Biology, Max-Planck-Institute for Biochemistry, Munich, Germany * Corresponding author; email: yanxy{at}sun5.ibp.ac.cn. The goal of our study was to raise monoclonal antibodies (mAbs) against endothelial cell surface proteins specific for tumor vasculature. Here, we describe the generation and intensive characterization of mAb AA98, including its functional properties, and its antigen identification. In our study, an enhanced mAb AA98-immunoreactivity was observed on stimulated human umbilical vein endothelial cells (HUVEC). In addition, mAb AA98 showed remarkably restricted immunoreactivity against intratumoral neovasculature compared to blood vessels of normal tissues. We identified the AA98-antigen as human CD146, an adhesion molecule belonging to the immunoglobulin superfamily. Data from in vitro experiments imply structural and signaling functions for endothelial CD146, however, the role of CD146 in vivo is largely unknown. Here, we show that mAb AA98 displays anti-angiogenic properties in vitro and in vivo. Proliferation and migration of HUVECs were inhibited by mAb AA98 as was angiogenesis in chicken chorioallantoic membrane (CAM) assays and tumor growth in three xenografted human tumor models in mice. Our data provide new insights into the function of CD146 on endothelial cells, validate CD146 as a novel target for antiangiogenic agents, and demonstrate that mAb AA98 has potential as a diagnostic and therapeutic agent in vascular and cancer biology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Zhang, L. Li, L. Feng, Y. Zhang, X. Zeng, J. Feng, D. Yang, C. Zheng, and X. Yan Elevated Levels of Soluble and Neutrophil CD146 in Active Systemic Vasculitis Lab Med, June 1, 2009; 40(6): 351 - 356. [Abstract] [Full Text] [PDF] N. Bardin, M. Blot-Chabaud, N. Despoix, A. Kebir, K. Harhouri, J.-P. Arsanto, L. Espinosa, P. Perrin, S. Robert, F. Vely, et al. CD146 and its Soluble Form Regulate Monocyte Transendothelial Migration Arterioscler Thromb Vasc Biol, May 1, 2009; 29(5): 746 - 753. [Abstract] [Full Text] [PDF] S. Bidlingmaier, J. He, Y. Wang, F. An, J. Feng, D. Barbone, D. Gao, B. Franc, V. C. 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Yan Anti-CD146 monoclonal antibody AA98 inhibits angiogenesis via suppression of nuclear factor-{kappa}B activation. Mol. Cancer Ther., November 1, 2006; 5(11): 2872 - 2878. [Abstract] [Full Text] [PDF] T. Ishida, R. K. Kundu, E. Yang, K.-i. Hirata, Y.-D. Ho, and T. Quertermous Targeted Disruption of Endothelial Cell-selective Adhesion Molecule Inhibits Angiogenic Processes in Vitro and in Vivo J. Biol. Chem., September 5, 2003; 278(36): 34598 - 34604. [Abstract] [Full Text] [PDF]

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