The epithelial-mesenchymal transition promotes transdifferentiation of subcutaneously implanted hepatic oval cells into mesenchymal tumor tissue

Stem Cells Dev. 2009 Nov;18(9):1293-8. doi: 10.1089/scd.2008.0321.

Abstract

Hepatic oval cells are thought to represent facultative hepatic epithelial stem cells in liver in which damage inhibits hepatocyte proliferation and liver regeneration. The LE/6 hepatic stem cell line was derived from the liver of male Sprague-Dawley rats fed a choline-deficient diet containing 0.1% ethionine. They are histochemically characterized by their expression of hepatocytic (hepPar1), cholangiocytic cytokeratin (CK19), hepatic progenitor cell (OV-6), and hematopoietic stem cell (c-kit) markers. In this study, we transplanted LE/6 cells by subcutaneous injection into adult female nude mice, and examined their engraftment and differentiation potential in the subcutaneous microenvironment in vivo. Our results demonstrated that following subcutaneous transplantation, differentiation of LE/6 cells into mesenchymal tumor tissue (MTT) was associated with reduced E-cadherin expression, upregulation of E-cadherin repressor molecules (Snail proteins), and increased expression of vimentin and N-cadherin, all of these events are characteristic of the epithelial-mesenchymal transition (EMT).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cadherins / metabolism
  • Cell Transdifferentiation*
  • Cell Transplantation / methods*
  • Cells, Cultured
  • Epithelium / pathology
  • Female
  • In Situ Hybridization, Fluorescence
  • Liver / cytology*
  • Male
  • Mesenchymoma / metabolism
  • Mesenchymoma / pathology
  • Mesenchymoma / ultrastructure
  • Mesoderm / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microscopy, Electron, Transmission
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology*
  • Neoplasms, Experimental / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Snail Family Transcription Factors
  • Transcription Factors / metabolism
  • Transplantation, Heterologous
  • Vimentin / metabolism

Substances

  • Cadherins
  • Snai2 protein, rat
  • Snail Family Transcription Factors
  • Transcription Factors
  • Vimentin