Loss of P-cadherin expression in hepatocellular carcinoma induces tumorigenicity
P-cadherin is a major contributor to cell-cell adhesion in epithelial tissues, playing pivotal roles in important morphogenetic and differentiation processes and in maintaining tissue integrity and homeostasis. Alterations of P-cadherin expression have been observed during the progression of several carcinomas where it appears to act as tumor suppressive or oncogenic in a contextdependent manner
The aim of this study was to assess P-cadherin expression and its role in hepatocellular carcinoma (HCC).
Material and methods: Quantitative PCR analysis revealed a significant downregulation of P-cadherin mRNA in 4 human HCC cell lines compared to primary human hepatocytes, and in human HCC tissues compared to corresponding non-malignant liver tissues. Immunohistochemical analysis of a tissue microarray containing matched pairs of HCC tissue and corresponding non-tumorous liver tissue of 69 patients confirmed reduced P-cadherin expression in 60% of cases. In 35 HCCs the P-cadherin immunosignal was completely lost. Correlation with clinicopathological characteristics revealed that these cases had significantly higher Ki67 labeling index. Furthermore, loss of P-cadherin expression significantly correlated with tumor staging but not with tumor grading. Functional analysis revealed a significant increase in proliferation after reduction of the basal P-cadherin expression levels in HCC cells via siRNA against P-cadherin.
Summary and Conclusion: Loss of P-cadherin expression in HCC induces tumorigenicity. Therefore, P-cadherin expression may serve as a prognostic marker and therapeutic target of this highly aggressive tumor.