Open AccessCellular plasticity of trans- and dedifferentiation markers in human hepatoma cells in vitro and in vivo
Author(s) -
Samir Jabari,
Matthias Meissnitzer,
Karl Quint,
Susanne Gahr,
TT Wissniowski,
Eckhart G. Hahn,
Daniel Neureiter,
Matthias Ocker
Publication year - 2009
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo_00000314
Subject(s) - biology , vimentin , embryonic stem cell , cd34 , progenitor cell , stem cell marker , stem cell , cell culture , cellular differentiation , cancer research , oncogene , mesenchymal stem cell , microbiology and biotechnology , cell , cell cycle , immunohistochemistry , immunology , gene , genetics
Tumor cells have the capability to trans- and to dedifferentiate, for example by reactivating embryonic development genes and stem cell characteristics. The aim of our study was to show the differential expression of stem- and progenitor cell markers in human hepatocellular carcinoma cell lines (HCC). Different human HCC cell lines (HUH7, HUH7 5-15, HUH7 pcDNA3.1, Hep3B and HepG2) were cultured under standard conditions in vitro or implanted subcutaneously (5x10(6) cells) in male NMRI mice. Specimens were characterized by quantitative real-time PCR, Western blotting, methylation-specific PCR and immunohistochemistry for markers of differentiation (cytokeratins, vimentin), embryonic development or stem cells (PTC, PDX-1, SHH, Thy1, c-kit, CD34, beta-catenin, Ki-67). The investigated HCC cell lines showed different patterns of marker expression allowing to distinguish four distinct groups: the classical cholangiocellular type (Huh-7, Huh-7 pcDNA3.1, Hep3B) with expression of CK7/19, beta-catenin and CD34; a dedifferentiated mesenchymal-proliferative type (Huh-7 5-15) characterized by CK19, Vimentin and Ki-67; a dedifferentiated embryonic-development type (Hep3B implanted in matrigel) with expression of CK19, beta-catenin and PTC and a classical HCC type (HepG2) showing CK18/19 and beta-catenin expression. HCC cell lines showed significantly different expression patterns of differentiation markers in a xenograft model. Furthermore, direct association of some markers was observed. The groups differ from each other in expression patterns, but also show that environmental factors play an important role in the behaviour of cells.