A Newly Established Murine Cell Line as a Model for Hepatocellular Cancer in Non-Alcoholic Steatohepatitis

Andreas Kroh*, Jeanette Walter, Herdit Schueler, Jochen Nolting, Roman Eickhoff, Daniel Heise, Ulf Peter Neumann, Thorsten Cramer, Tom Florian Ulmer, Athanassios Fragoulis

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Non-alcoholic steatohepatitis (NASH) has become a major risk factor for hepatocellular cancer (HCC) due to the worldwide increasing prevalence of obesity. However, the pathophysiology of NASH and its progression to HCC is incompletely understood. Thus, the aim of this study was to generate a model specific NASH-derived HCC cell line. A murine NASH-HCC model was conducted and the obtained cancer cells (N-HCC25) were investigated towards chromosomal aberrations, the expression of cell type-specific markers, dependency on nutrients, and functional importance of mTOR. N-HCC25 exhibited several chromosomal aberrations as compared to healthy hepatocytes. Hepatocytic (HNF4), EMT (Twist, Snail), and cancer stem cell markers (CD44, EpCAM, CK19, Sox9) were simultaneously expressed in these cells. Proliferation highly depended on the supply of glucose and FBS, but not glutamine. Treatment with a second generation mTOR inhibitor (KU-0063794) resulted in a strong decrease of cell growth in a dose-dependent manner. In contrast, a first generation mTOR inhibitor (Everolimus) only slightly reduced cell proliferation. Cell cycle analyses revealed that the observed growth reduction was most likely due to G(1)/G(0) cell cycle arrest. These results indicate that N-HCC25 is a highly proliferative HCC cell line from a NASH background, which might serve as a suitable in vitro model for future investigations of NASH-derived HCC.

Original languageEnglish
Article number5658
Number of pages23
JournalInternational journal of molecular sciences
Volume20
Issue number22
DOIs
Publication statusPublished - Nov 2019

Keywords

  • non-alcoholic steatohepatitis
  • hepatocellular carcinoma
  • cell line
  • mTOR
  • Everolimus
  • KU-0063794
  • LIVER-TRANSPLANT RECIPIENTS
  • MAMMALIAN TARGET
  • HEPATITIS-C
  • SCORING SYSTEM
  • RENAL-FUNCTION
  • RISK-FACTORS
  • CARCINOMA
  • MTOR
  • EVEROLIMUS
  • GLUTAMINE

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