Expression of T-cadherin in tumor cells influences invasive potential of human hepatocellular carcinoma.
Overexpression of T-cadherin (T-cad) transcripts occurs in approximately 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
Philippe
P
Inserm U602, Université Paris XI, Villejuif, France.
Saffroy
Raphael
R
Chenailler
Catherine
C
Franc
Brigitte
B
Gentile
Carla
C
Rubinstein
Eric
E
Resink
Therese
T
Debuire
Brigitte
B
Piatier-Tonneau
Dominique
D
Lemoine
Antoinette
A
D000818:Animals; D015820:Cadherins / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D018929:Cell Culture Techniques; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D017931:DNA Primers; D042783:Endothelial Cells / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000502:physiology*; D008113:Liver Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000235:genetics; D011817:Rabbits; D014158:Transcription, Genetic; D014162:Transfection; D014945:Wound Healing
D015820:Cadherins; D017931:DNA Primers; C099972:H-cadherin; D034741:RNA, Small Interfering