c-Met inhibitor upregulates E-cadherin, which is lost in portal vein tumor thrombus of hepatocellular carcinoma.

Abstract

Aim: Portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) is an essential therapeutic and prognostic factor. E-cadherin plays a crucial role in adhesive properties and intercellular interaction in various cancer tissues, including HCC, but the expression profile and functional contribution of E-cadherin in PVTT remain unknown. This study aimed to analyze the expression of E-cadherin in the main tumor tissue and PVTT tissue of HCC, and evaluate the functional roles of E-cadherin in PVTT formation.

Methods: A retrospective analysis was performed using the medical records of patients who underwent liver resection for HCC with PVTT, analyzing tissue specimens from 1995 to 2016. E-cadherin expression is evaluated using immunohistochemistry and western blot. The study also uses a c-Met inhibitor to explore its impact on E-cadherin expression in vitro and in vivo using cell lines and a tumor xenograft mouse model.

Results: The results revealed a reduced E-cadherin expression in PVTT tissue than in the main tumor tissue. The inhibition of c-Met activation, frequently detected in HCC, upregulated E-cadherin expression in HCC cell lines. Furthermore, treatment with c-Met inhibitors induced changes in epithelial morphology, and inhibited migration and invasion of HCC cell lines.

Conclusions: This study demonstrates the downregulation of E-cadherin in PVTT, and underscores the potential of c-Met inhibition in upregulating E-cadherin and inhibiting metastatic behavior. Understanding the significance of E-cadherin and c-Met in HCC progression provides a foundation for future clinical investigations into the therapeutic effects of c-Met inhibitors on PVTT in HCC patients.