Expression of T-cadherin in tumor cells influences invasive potential of human hepatocellular carcinoma

• Published in: The FASEB journal Vol. 20; no. 13; pp. 2291 - 2301
• Main Authors: Riou, Philippe, Saffroy, Raphael, Chenailler, Catherine, Franc, Brigitte, Gentile, Carla, Rubinstein, Eric, Resink, Therese, Debuire, Brigitte, Piatier-Tonneau, Dominique, Lemoine, Antoinette
• Format: Journal Article
• Language: English
• Published: United States The Federation of American Societies for Experimental Biology 01.11.2006
• Subjects: Animals; Cadherins - genetics; Carcinoma, Hepatocellular - pathology; Cell Culture Techniques; Cell Division; Cell Line, Tumor; Cell Movement; DNA Primers; Endothelial Cells - physiology; Fibroblasts - physiology; Hepatocytes - physiology; Humans; Liver - cytology; Liver - physiology; Liver Neoplasms - pathology; Neoplasm Invasiveness; Rabbits; RNA, Small Interfering - genetics; Transcription, Genetic; Transfection; Wound Healing
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.06-6085com

Overexpression of T-cadherin (T-cad) transcripts occurs in [almost equal to]50% of human hepatocellular carcinomas (HCCs). To elucidate T-cad functions in HCC, we examined T-cad protein expression in normal and tumoral human livers and hepatoma cell lines and investigated its influence on invasive potential of HCC using RNA interference silencing of T-cad expression in Mahlavu cells. Whereas T-cad expression was restricted to endothelial cells (EC) from large blood vessels in normal livers, it was up-regulated in sinusoidal EC from 8/15 invasive HCCs. Importantly, in three of them (38%) T-cad was detected in tumor cells within regions in which E-cadherin expression was absent. Among six hepatoma cell lines, only Mahlavu expressed T-cad but not E-cadherin. T-cad exhibited a globally punctuate distribution in quiescent Mahlavu and additionally it concentrated at the leading edge of migrating cells. Matrigel invasion assay revealed that Mahlavu possess a high invasive potential that was significantly inhibited by T-cad silencing. Wound healing and random motility assays demonstrated that inhibition of T-cad expression in Mahlavu significantly reduced their motility. We propose that T-cad expression in tumor cells might occur by cadherin-switching during epithelial-mesenchymal transition and may represent an additional mechanism contributing to HCC metastasis.--Riou, P., Saffroy, R., Chenailler, C., Franc, B., Gentile, C., Rubinstein, E., Resink, T., Debuire, B., Piatier-Tonneau, D., Lemoine, A. Expression of T-cadherin in tumor cells influences invasive potential of human hepatocellular carcinoma.