Proapoptotic function of integrin β 3 in human hepatocellular carcinoma cells

Yanhua Wu, Jie Zuo, Guoqing Ji, Hexige Saiyin, Xing Liu, Feiyu Yin, Ning Cao, Yunfei Wen, Jian-Jian Li, Long Yu

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Purpose: This study evaluates the proapoptotic function of integrin β 3 in human hepatocellular carcinoma (HCC). Experimental Design: The expression of integrin β 3 in 67 HCC specimens paired with corresponding neighboring nontumorous tissue was studied by quantitative real-time PCR and Western blot. The proapoptotic function of integrin β 3 in SMMC-7721 human hepatoma cells overexpressing ITGB3 (gene coding integrin β 3) was determined through colony formation, serum starvation, and anoikis assay. Results: Compared with neighboring pathologically normal liver tissue, -60% of the HCC specimens showed a significant down-regulated level of integrin β 3 expression. Transient expression of integrin β 3 in SMMC-7721 resulted in an enhanced level of apoptosis and suppression of colony formation. Cell growth inhibition on serum/ligand deprivation and incidences of anoikis were remarkably increased in SMMC-7721 with stable expression of integrin β 3 in comparison with vector control transfectants. In addition, expression of fibrinogen and vitronectin, two native ligands for integrin α vβ 3 in liver, was inhibited, which was correlated with the decreased integrin β 3 expression. Replenishing these ligands to the starved SMMC-7721 stable transfectants effectively restored the proapoptotic function of integrin β 3. Conclusions: Down-regulation of integrin β 3 and its ligands in liver is related to the aggressive growth of HCC. Thus, reconstitution of integrin in HCC may be a potential therapeutic approach to inhibit aggressive growth of liver cancer.

Original languageEnglish (US)
Pages (from-to)60-69
Number of pages10
JournalClinical Cancer Research
Volume15
Issue number1
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Wu, Y., Zuo, J., Ji, G., Saiyin, H., Liu, X., Yin, F., Cao, N., Wen, Y., Li, J-J., & Yu, L. (2009). Proapoptotic function of integrin β 3 in human hepatocellular carcinoma cells. Clinical Cancer Research, 15(1), 60-69. https://doi.org/10.1158/1078-0432.CCR-08-1028