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Cooperation between integrin alpha(5) and tetraspan TM4SF5 regulates VEGF-mediated angiogenic activity

Cited 44 time in Web of Science Cited 44 time in Scopus
Authors
Choi, Suyong; Lee, Sin-Ae; Kwak, Tae Kyoung; Kim, Hyeon Jung; Lee, Mi Ji; Ye, Sang-Kyu; Kim, Sung-Hoon; Kim, Semi; Lee, Jung Weon
Issue Date
2009-02
Publisher
American Society of Hematology
Citation
BLOOD Vol.113 No.8, pp. 1845-1855
Keywords
복합학
Abstract
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 alpha(5) on the cell surface for VEGF induction, and preincubation with anti-integrin alpha(5) antibody abolished TM4SF5-mediated VEGF expression and secretion. TM4SF5-mediated effects required integrin alpha(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 alpha(5) expression, vessel formation, and signaling activity, which were inhibited by administration of anti integrin alpha(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 alpha(5) of epithelial cells. (Blood. 2009;113:1845-1855)
ISSN
0006-4971
Language
English
URI
https://hdl.handle.net/10371/82059
DOI
https://doi.org/10.1182/blood-2008-05-160671
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College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Journal Papers (저널논문_약학과)
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