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Differential propagation of stroma and cancer stem cells dictates tumorigenesis and multipotency

Glioblastoma Multiforme (GBM) is characterized by high cancer cell heterogeneity and the presence of a complex tumor microenvironment. Those factors are a key obstacle for the treatment of this tumor type. To model the disease in mice, the current strategy is to grow GBM cells in serum-free non-adhe...

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Autores principales: Behnan, J, Stangeland, B, Hosainey, S A M, Joel, M, Olsen, T K, Micci, F, Glover, J C, Isakson, P, Brinchmann, J E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290038/
https://www.ncbi.nlm.nih.gov/pubmed/27345406
http://dx.doi.org/10.1038/onc.2016.230
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author Behnan, J
Stangeland, B
Hosainey, S A M
Joel, M
Olsen, T K
Micci, F
Glover, J C
Isakson, P
Brinchmann, J E
author_facet Behnan, J
Stangeland, B
Hosainey, S A M
Joel, M
Olsen, T K
Micci, F
Glover, J C
Isakson, P
Brinchmann, J E
author_sort Behnan, J
collection PubMed
description Glioblastoma Multiforme (GBM) is characterized by high cancer cell heterogeneity and the presence of a complex tumor microenvironment. Those factors are a key obstacle for the treatment of this tumor type. To model the disease in mice, the current strategy is to grow GBM cells in serum-free non-adherent condition, which maintains their tumor-initiating potential. However, the so-generated tumors are histologically different from the one of origin. In this work, we performed high-throughput marker expression analysis and investigated the tumorigenicity of GBM cells enriched under different culture conditions. We identified a marker panel that distinguished tumorigenic sphere cultures from non-tumorigenic serum cultures (high CD56, SOX2, SOX9, and low CD105, CD248, αSMA). Contrary to previous work, we found that ‘mixed cell cultures' grown in serum conditions are tumorigenic and express cancer stem cell (CSC) markers. As well, 1% serum plus bFGF and TGF-α preserved the tumorigenicity of sphere cultures and induced epithelial-to-mesenchymal transition gene expression. Furthermore, we identified 12 genes that could replace the 840 genes of The Cancer Genome Atlas (TCGA) used for GBM-subtyping. Our data suggest that the tumorigenicity of GBM cultures depend on cell culture strategies that retain CSCs in culture rather than the presence of serum in the cell culture medium.
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spelling pubmed-52900382017-02-10 Differential propagation of stroma and cancer stem cells dictates tumorigenesis and multipotency Behnan, J Stangeland, B Hosainey, S A M Joel, M Olsen, T K Micci, F Glover, J C Isakson, P Brinchmann, J E Oncogene Original Article Glioblastoma Multiforme (GBM) is characterized by high cancer cell heterogeneity and the presence of a complex tumor microenvironment. Those factors are a key obstacle for the treatment of this tumor type. To model the disease in mice, the current strategy is to grow GBM cells in serum-free non-adherent condition, which maintains their tumor-initiating potential. However, the so-generated tumors are histologically different from the one of origin. In this work, we performed high-throughput marker expression analysis and investigated the tumorigenicity of GBM cells enriched under different culture conditions. We identified a marker panel that distinguished tumorigenic sphere cultures from non-tumorigenic serum cultures (high CD56, SOX2, SOX9, and low CD105, CD248, αSMA). Contrary to previous work, we found that ‘mixed cell cultures' grown in serum conditions are tumorigenic and express cancer stem cell (CSC) markers. As well, 1% serum plus bFGF and TGF-α preserved the tumorigenicity of sphere cultures and induced epithelial-to-mesenchymal transition gene expression. Furthermore, we identified 12 genes that could replace the 840 genes of The Cancer Genome Atlas (TCGA) used for GBM-subtyping. Our data suggest that the tumorigenicity of GBM cultures depend on cell culture strategies that retain CSCs in culture rather than the presence of serum in the cell culture medium. Nature Publishing Group 2017-01-26 2016-06-27 /pmc/articles/PMC5290038/ /pubmed/27345406 http://dx.doi.org/10.1038/onc.2016.230 Text en Copyright © 2017 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Original Article
Behnan, J
Stangeland, B
Hosainey, S A M
Joel, M
Olsen, T K
Micci, F
Glover, J C
Isakson, P
Brinchmann, J E
Differential propagation of stroma and cancer stem cells dictates tumorigenesis and multipotency
title Differential propagation of stroma and cancer stem cells dictates tumorigenesis and multipotency
title_full Differential propagation of stroma and cancer stem cells dictates tumorigenesis and multipotency
title_fullStr Differential propagation of stroma and cancer stem cells dictates tumorigenesis and multipotency
title_full_unstemmed Differential propagation of stroma and cancer stem cells dictates tumorigenesis and multipotency
title_short Differential propagation of stroma and cancer stem cells dictates tumorigenesis and multipotency
title_sort differential propagation of stroma and cancer stem cells dictates tumorigenesis and multipotency
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290038/
https://www.ncbi.nlm.nih.gov/pubmed/27345406
http://dx.doi.org/10.1038/onc.2016.230
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