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

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dc.contributor.authorChoi, Suyong-
dc.contributor.authorLee, Sin-Ae-
dc.contributor.authorKwak, Tae Kyoung-
dc.contributor.authorKim, Hyeon Jung-
dc.contributor.authorLee, Mi Ji-
dc.contributor.authorYe, Sang-Kyu-
dc.contributor.authorKim, Sung-Hoon-
dc.contributor.authorKim, Semi-
dc.contributor.authorLee, Jung Weon-
dc.date.accessioned2010-06-25T07:14:27Z-
dc.date.available2010-06-25T07:14:27Z-
dc.date.issued2008-11-28-
dc.identifier.citationBlood. 2009;113(8):1845-1855en
dc.identifier.issn1528-0020 (Electronic)-
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19036703-
dc.identifier.urihttp://bloodjournal.hematologylibrary.org/cgi/reprint/113/8/1845.pdf-
dc.identifier.urihttp://hdl.handle.net/10371/67828-
dc.description.abstractTetraspan 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.en
dc.language.isoenen
dc.publisherAmerican Society of Hematologyen
dc.subjectAnimalsen
dc.subjectAntibodies/pharmacologyen
dc.subjectAorta/cytologyen
dc.subjectCarcinoma, Hepatocellular/*blood supply/metabolismen
dc.subjectCell Line, Tumoren
dc.subjectCulture Media, Conditioned/pharmacologyen
dc.subjectEpithelial Cells/cytology/metabolismen
dc.subjectFocal Adhesion Protein-Tyrosine Kinases/metabolismen
dc.subjectHumansen
dc.subjectIntegrin alpha5/immunology/*metabolismen
dc.subjectLiver Neoplasms/*blood supply/metabolismen
dc.subjectMaleen
dc.subjectMembrane Proteins/genetics/*metabolismen
dc.subjectMiceen
dc.subjectMice, Inbred BALB Cen
dc.subjectMice, Nudeen
dc.subjectNeoplasm Transplantationen
dc.subjectNeovascularization, Physiologic/*physiologyen
dc.subjectProtein-Tyrosine Kinases/metabolismen
dc.subjectSTAT3 Transcription Factor/metabolismen
dc.subjectSignal Transduction/physiologyen
dc.subjectTransfectionen
dc.subjectVascular Endothelial Growth Factor A/genetics/immunology/*metabolismen
dc.titleCooperation between integrin alpha5 and tetraspan TM4SF5 regulates VEGF-mediated angiogenic activityen
dc.typeArticleen
dc.contributor.AlternativeAuthor최수용-
dc.contributor.AlternativeAuthor이신애-
dc.contributor.AlternativeAuthor곽태경-
dc.contributor.AlternativeAuthor김현정-
dc.contributor.AlternativeAuthor이미지-
dc.contributor.AlternativeAuthor예상규-
dc.contributor.AlternativeAuthor김성훈-
dc.contributor.AlternativeAuthor김세미-
dc.contributor.AlternativeAuthor이정원-
dc.identifier.doi10.1182/blood-2008-05-160671-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
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