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Oncogene. 2017 Jan 26;36(4):570-584. doi: 10.1038/onc.2016.230. Epub 2016 Jun 27.

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

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Norwegian Center for Stem Cell Research, Department of Immunology, Oslo University Hospital, Oslo, Norway.
Department of Molecular Medicine, Institute of Basic Medical Sciences, The Medical Faculty, University of Oslo, Oslo, Norway.
Department of Neurosurgery, Institute for Surgical Research, Oslo University Hospital, Oslo, Norway.
Department of Neurosurgery, St. Olavs University Hospital, Trondheim, Norway.
Department of Neurosurgery, Oslo University Hospital, Oslo, Norway.
Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway.
Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.


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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