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Blood, 19 February 2009, Vol. 113, No. 8, pp. 1845-1855. Prepublished online as a Blood First Edition Paper on November 25, 2008; DOI 10.1182/blood-2008-05-160671. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-05-160671v1 113/8/1845    most recent 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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Choi, S. Articles by Lee, J. W. Search for Related Content PubMed PubMed Citation Articles by Choi, S. Articles by Lee, J. W. Related Collections Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  VASCULAR BIOLOGY Cooperation between integrin 5 and tetraspan TM4SF5 regulates VEGF-mediated angiogenic activity Suyong Choi1,2, Sin-Ae Lee1,3, Tae Kyoung Kwak1,2, Hyeon Jung Kim1, Mi Ji Lee1,4, Sang-Kyu Ye5, Sung-Hoon Kim6, Semi Kim7, and Jung Weon Lee13 1 Cancer Research Institute, Cell Dynamics Research Center, and Departments of 2 Tumor Biology, 3 Molecular & Clinical Oncology, 4 Biomedical Sciences, and 5 Pharmacology, College of Medicine, Seoul National University, Seoul; 6 Cancer Preventive Material Development Center (CPMRC), College of Oriental Medicine, Kyunghee University, Seoul; and 7 Korea Research Institute of Bioscience & Biotechnology (KRIBB), Taejon, South Korea Tetraspan TM4SF5 is highly expressed in a diverse number of tumor types. Here we explore the mechanistic roles of TM4SF5 in angiogenesis. We found that TM4SF5 overexpression correlates with vascular endothelial growth factor (VEGF) expression in SNU449 hepatocytes and with vessel formation in clinical hepatocarcinoma samples. Conditioned media from TM4SF5-expressing cells enhanced viability and tube formation of primary human umbilical vein endothelial cells, and outgrowth of endothelial cells from aorta ring segments, which was abolished by treatment with an anti-VEGF antibody. TM4SF5 retained integrin 5 on the cell surface for VEGF induction, and preincubation with anti–integrin 5 antibody abolished TM4SF5-mediated VEGF expression and secretion. TM4SF5-mediated effects required integrin 5, c-Src, and signal transducer and activator of transcription 3 (STAT3). In addition, tumors from nude mice injected with TM4SF5-expressing cells and from clinical human hepatocarcinoma tissues showed enhanced integrin 5 expression, vessel formation, and signaling activity, which were inhibited by administration of anti–integrin 5 or -VEGF antibody. This study suggests that TM4SF5 facilitates angiogenesis of neighboring endothelial cells through VEGF induction, mediated by cooperation between TM4SF5 and integrin 5 of epithelial cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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