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Int J Clin Exp Pathol. 2014 Aug 15;7(9):6125-32. eCollection 2014.

Downregulation of P-cadherin expression in hepatocellular carcinoma induces tumorigenicity.

Author information

1
Department of Oral and Maxillofacial Surgery, University Hospital Regensburg Germany.
2
Department of Internal Medicine I, University Hospital Regensburg Germany.
3
Tissue Bank O.B. HTCR and Center for Liver Cell Research, Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Grosshadern Hospital, Ludwig-Maximilians-University, Munich Germany;
4
Institute of Pathology, University Erlangen-Nuremberg Germany.

Abstract

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 context-dependent manner. Here, we found a significant downregulation of P-cadherin in hepatocellular carcinoma (HCC) cell lines and tissues compared to primary human hepatocytes and non-malignant liver tissues. Combined 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 more than half of the cases. In 35 human HCC tissues, the P-cadherin immunosignal was completely lost which correlated with tumor staging and proliferation. Also in vitro, P-cadherin suppression in HCC cells via siRNA induced proliferation compared to cells transfected with control-siRNA. In summary, downregulation of P-cadherin expression appears to induce tumorigenicity in HCC. Therefore, P-cadherin expression may serve as a prognostic marker and therapeutic target of this highly aggressive tumor.

KEYWORDS:

P-cadherin; hepatocellular carcinoma; proliferation; tumor staging

PMID:
25337260
PMCID:
PMC4203231
[Indexed for MEDLINE]
Free PMC Article

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