Proapoptotic Function of Integrin β3 in Human Hepatocellular Carcinoma Cells

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 v β 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 β 3 in HCC may be a potential therapeutic approach to inhibit aggressive growth of liver cancer.