Mechanical stiffness of liver tissues in relation to integrin β1 expression may influence the development of hepatic cirrhosis and hepatocellular carcinoma

Abstract

Background and objectives: Increased rigidity of the extracellular matrix (ECM) is commonly associated with hepatocellular carcinoma (HCC). The purpose of this study was to quantitate the mechanical stiffness of various hepatic tissues, evaluate integrin β1 expression, and investigate the correlation between these two factors in the development of HCC.

Methods: Twenty-three normal specimens, 152 cases of cirrhosis, and 105 cases of HCC were included in this study. The mechanical stiffness of the ECM of each specimen was detected using atomic force microscopy to calculate elastic modulus (E) values. Integrin β1 expression was also evaluated using semi-quantitative RT-PCR, western blot, and immunohistochemistry. Expression of integrin β1 in HepG2 cells plated on substrates with different mechanical stiffnesses was also evaluated.

Results: A positive correlation between ECM mechanical stiffness and integrin β1 expression was detected. Expression of integrin β1 also correlated with Edmondson pathologic grade, encapsulation, metastasis, and HBV infection (P < 0.01). In vitro, expression of integrin β1 by HepG2 cells was also significantly higher when the cells were plated on stiffer substrates.

Conclusions: Expression of integrin β1 is regulated by the mechanical stiffness of the ECM, and correlates with the invasion and metastasis events of HCC in patients with cirrhosis.