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Establishing normal metabolism and differentiation in hepatocellular carcinoma cells by culturing in adult human serum
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 differen...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076254/ https://www.ncbi.nlm.nih.gov/pubmed/30076349 http://dx.doi.org/10.1038/s41598-018-29763-2 |
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author | Steenbergen, Rineke Oti, Martin ter Horst, Rob Tat, Wilson Neufeldt, Chris Belovodskiy, Alexandr Chua, Tiing Tiing Cho, Woo Jung Joyce, Michael Dutilh, Bas E. Tyrrell, D. Lorne |
author_facet | Steenbergen, Rineke Oti, Martin ter Horst, Rob Tat, Wilson Neufeldt, Chris Belovodskiy, Alexandr Chua, Tiing Tiing Cho, Woo Jung Joyce, Michael Dutilh, Bas E. Tyrrell, D. Lorne |
author_sort | Steenbergen, Rineke |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6076254 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60762542018-08-07 Establishing normal metabolism and differentiation in hepatocellular carcinoma cells by culturing in adult human serum Steenbergen, Rineke Oti, Martin ter Horst, Rob Tat, Wilson Neufeldt, Chris Belovodskiy, Alexandr Chua, Tiing Tiing Cho, Woo Jung Joyce, Michael Dutilh, Bas E. Tyrrell, D. Lorne Sci Rep Article 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. Nature Publishing Group UK 2018-08-03 /pmc/articles/PMC6076254/ /pubmed/30076349 http://dx.doi.org/10.1038/s41598-018-29763-2 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Steenbergen, Rineke Oti, Martin ter Horst, Rob Tat, Wilson Neufeldt, Chris Belovodskiy, Alexandr Chua, Tiing Tiing Cho, Woo Jung Joyce, Michael Dutilh, Bas E. Tyrrell, D. Lorne Establishing normal metabolism and differentiation in hepatocellular carcinoma cells by culturing in adult human serum |
title | Establishing normal metabolism and differentiation in hepatocellular carcinoma cells by culturing in adult human serum |
title_full | Establishing normal metabolism and differentiation in hepatocellular carcinoma cells by culturing in adult human serum |
title_fullStr | Establishing normal metabolism and differentiation in hepatocellular carcinoma cells by culturing in adult human serum |
title_full_unstemmed | Establishing normal metabolism and differentiation in hepatocellular carcinoma cells by culturing in adult human serum |
title_short | Establishing normal metabolism and differentiation in hepatocellular carcinoma cells by culturing in adult human serum |
title_sort | establishing normal metabolism and differentiation in hepatocellular carcinoma cells by culturing in adult human serum |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076254/ https://www.ncbi.nlm.nih.gov/pubmed/30076349 http://dx.doi.org/10.1038/s41598-018-29763-2 |
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