Format

Send to

Choose Destination
Sci Rep. 2018 Aug 3;8(1):11685. doi: 10.1038/s41598-018-29763-2.

Establishing normal metabolism and differentiation in hepatocellular carcinoma cells by culturing in adult human serum.

Author information

1
Li Ka Shing Institute of Virology, Dept. of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada. rineke.steenbergen@ualberta.ca.
2
Carlos Chagas Filho Biophysics Institute (IBCCF), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
3
Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
4
Li Ka Shing Institute of Virology, Dept. of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
5
Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, The Netherlands.

Abstract

Tissue culture medium routinely contains fetal bovine serum (FBS). Here we show that culturing human hepatoma cells in their native, adult serum (human serum, HS) results in the restoration of key morphological and metabolic features of normal liver cells. When moved to HS, these cells show differential transcription of 22-32% of the genes, stop proliferating, and assume a hepatocyte-like morphology. Metabolic analysis shows that the Warburg-like metabolic profile, typical for FBS-cultured cells, is replaced by a diverse metabolic profile consistent with in vivo hepatocytes, including the formation of large lipid and glycogen stores, increased glycogenesis, increased beta-oxidation and ketogenesis, and decreased glycolysis. Finally, organ-specific functions are restored, including xenobiotics degradation and secretion of bile, VLDL and albumin. Thus, organ-specific functions are not necessarily lost in cell cultures, but might be merely suppressed in FBS. The effect of serum is often overseen in cell culture and we provide a detailed study in the changes that occur and provide insight in some of the serum components that may play a role in the establishment of the differentiated phenotype.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center