TY - JOUR
T1 - Proapoptotic function of integrin β 3 in human hepatocellular carcinoma cells
AU - Wu, Yanhua
AU - Zuo, Jie
AU - Ji, Guoqing
AU - Saiyin, Hexige
AU - Liu, Xing
AU - Yin, Feiyu
AU - Cao, Ning
AU - Wen, Yunfei
AU - Li, Jian Jian
AU - Yu, Long
PY - 2009/1/1
Y1 - 2009/1/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-08-1028
DO - 10.1158/1078-0432.CCR-08-1028
M3 - Article
C2 - 19118033
AN - SCOPUS:58949101974
SN - 1078-0432
VL - 15
SP - 60
EP - 69
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 1
ER -