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Cooperation between integrin alpha5 and tetraspan TM4SF5 regulates VEGF-mediated angiogenic activity

Cited 43 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
2008-11-28
Publisher
American Society of Hematology
Citation
Blood. 2009;113(8):1845-1855
Keywords
AnimalsAntibodies/pharmacologyAorta/cytologyCarcinoma, Hepatocellular/*blood supply/metabolismCell Line, TumorCulture Media, Conditioned/pharmacologyEpithelial Cells/cytology/metabolismFocal Adhesion Protein-Tyrosine Kinases/metabolismHumansIntegrin alpha5/immunology/*metabolismLiver Neoplasms/*blood supply/metabolismMaleMembrane Proteins/genetics/*metabolismMiceMice, Inbred BALB CMice, NudeNeoplasm TransplantationNeovascularization, Physiologic/*physiologyProtein-Tyrosine Kinases/metabolismSTAT3 Transcription Factor/metabolismSignal Transduction/physiologyTransfectionVascular Endothelial Growth Factor A/genetics/immunology/*metabolism
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.
ISSN
1528-0020 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19036703

http://bloodjournal.hematologylibrary.org/cgi/reprint/113/8/1845.pdf

http://hdl.handle.net/10371/67828
DOI
https://doi.org/10.1182/blood-2008-05-160671
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College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
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