title: Downregulation of P-cadherin expression in hepatocellular carcinoma induces tumorigenicity.
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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Hospital Regensburg Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Bauer
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Valletta
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Hospital Regensburg Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Bauer
authors.affiliation: 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;
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Thasler
authors.affiliation: Institute of Pathology, University Erlangen-Nuremberg Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Müller
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Hospital Regensburg Germany.
authors.forename: Torsten E
authors.initials: TE
authors.lastname: Reichert
authors.affiliation: Department of Internal Medicine I, University Hospital Regensburg Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Hellerbrand
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D034622:RNA Interference; D046888:Tissue Array Analysis; D014162:Transfection
chemical_list: C512197:CDH3 protein, human; D015820:Cadherins
keywords: P-cadherin; hepatocellular carcinoma; proliferation; tumor staging