Cooperation between integrin α5 and tetraspan TM4SF5 regulates VEGF-mediated angiogenic activity

Suyong Choi, Sin Ae Lee, Tae Kyoung Kwak, Hyeon Jung Kim, Mi Ji Lee, Sang Kyu Ye, Sung Hoon Kim, Semi Kim, Jung Weon Lee

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

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 hepatocarci-noma samples. Conditioned media from TM4SF5-expressing cells enhanced viability and tube formation of primary human umbilical vein endothelial cells, and out-growth of endothelial cells from aorta ring segments, which was abolished by treatment with an anti-VEGF antibody. TM4SF5 retained integrin α5 on the cell surface for VEGF induction, and preincubation with anti-integrin α5 antibody abolished TM4SF5-mediated VEGF expression and secretion. TM4SF5-mediated effects required integrin α5, 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 α5 expression, vessel formation, and signaling activity, which were inhibited by administration of anti-integrin α5 or -VEGF antibody. This study suggests that TM4SF5 facilitates angio-genesis of neighboring endothelial cells through VEGF induction, mediated by cooperation between TM4SF5 and integrin α5 of epithelial cells.

Original languageEnglish (US)
Pages (from-to)1845-1855
Number of pages11
JournalBlood
Volume113
Issue number8
DOIs
StatePublished - Feb 19 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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