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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1234-1242. Prepublished online as a Blood First Edition Paper on April 4, 2006; DOI 10.1182/blood-2005-10-4296. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-10-4296v1 108/4/1234    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 Takahashi, T. Articles by Daniel, T. O Search for Related Content PubMed PubMed Citation Articles by Takahashi, T. Articles by Daniel, T. O Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 7, 2005 Accepted March 15, 2006 A monoclonal antibody against CD148, a receptor-like tyrosine phosphatase, inhibits endothelial cell growth and angiogenesis Takamune Takahashi*, Keiko Takahashi, Raymond L Mernaugh, Nobuo Tsuboi, Hua Liu, and Thomas O Daniel Division of Nephrology, Vanderbilt University School of Medicine, Nashville, TN, USA Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA Division of Nephrology, Vanderbilt University School of Medicine, Nashville, TN, USA; Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA * Corresponding author; email: takamune.takahashi{at}vanderbilt.edu. Angiogenesis contributes to a wide range of neoplastic, ischemic and inflammatory disorders. Definition of the intrinsic molecular controls in angiogenic vessel growth promises novel therapeutic approaches for angiogenesis-related diseases. CD148 (also named DEP-1/PTP) is a receptor-like protein tyrosine phosphatase which is abundantly expressed in vascular endothelial cells. To explore a role of CD148 in endothelial vessel formation, we generated a monoclonal antibody, Ab1, against the ectodomain sequence of CD148, and examined its effects on endothelial cell growth and vessel formation. Here we report that a bivalent, but not a monovalent, form of the Ab1 antibody inhibits endothelial cell growth and blocks angiogenesis in mouse cornea in vivo. We further demonstrate that: 1) bivalent Ab1 arrests cell cycle progression of CD148-transfected CHO cells at G0/G1 phase, 2) co-expression of catalytically inactive CD148 mutants attenuates the Ab1 cell growth inhibition, and 3) bivalent Ab1 suppresses phosphorylation of ERK1/2 kinases and Met tyrosine kinase as activated CD148 does, with an increase in CD148 associated tyrosine phosphatase activity. Taken together, these findings demonstrate that Ab1-induced ectodomain oligomerization arrests endothelial cell growth through catalytic activity of the CD148 cytoplasmic domain. The present study defines CD148 as a valuable molecular target for anti-angiogenesis therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. L. Sallee and K. Burridge Density-enhanced Phosphatase 1 Regulates Phosphorylation of Tight Junction Proteins and Enhances Barrier Function of Epithelial Cells J. Biol. Chem., May 29, 2009; 284(22): 14997 - 15006. [Abstract] [Full Text] [PDF] A. E. Toland, L. S. Rozek, S. Presswala, G. Rennert, and S. B. Gruber PTPRJ Haplotypes and Colorectal Cancer Risk Cancer Epidemiol. Biomarkers Prev., October 1, 2008; 17(10): 2782 - 2785. [Abstract] [Full Text] [PDF] M. J. Telen Role of Adhesion Molecules and Vascular Endothelium in the Pathogenesis of Sickle Cell Disease Hematology, January 1, 2007; 2007(1): 84 - 90. [Abstract] [Full Text] [PDF]

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