A novel model of liver cancer stem cells developed from induced pluripotent stem cells

Br J Cancer. 2020 Apr;122(9):1378-1390. doi: 10.1038/s41416-020-0792-z. Epub 2020 Mar 17.

Abstract

Background: Liver cancer is the second most common cause of cancer-related death. Every type of tumours including liver cancer contains cancer stem cells (CSCs). To date, the molecular mechanism regulating the development of liver CSCs remains unknown.

Methods: In this study, we tried to generate a new model of liver CSCs by converting mouse induced pluripotent stem cells (miPSCs) with hepatocellular carcinoma (HCC) cell line Huh7 cells conditioned medium (CM). miPSCs treated with CM were injected into the liver of BALB/c nude mice. The developed tumours were then excised and analysed.

Results: The primary cultured cells from the malignant tumour possessed self-renewal capacity, differentiation potential and tumorigenicity in vivo, which were found rich in liver cancer-associated markers as well as CSC markers.

Conclusions: We established a model of liver CSCs converting from miPS and showed different stages of stemness during conversion process. Our CSC model will be important to assess the molecular mechanisms necessary to develop liver CSCs and could help in defeating liver cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / drug effects*
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Self Renewal / drug effects
  • Culture Media, Conditioned / metabolism
  • Culture Media, Conditioned / pharmacology*
  • Humans
  • Induced Pluripotent Stem Cells / drug effects*
  • Induced Pluripotent Stem Cells / pathology
  • Liver / drug effects
  • Liver / pathology
  • Liver Neoplasms / etiology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Neoplastic Stem Cells / drug effects
  • Signal Transduction / drug effects

Substances

  • Culture Media, Conditioned