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Cell Rep. 2017 Jan 24;18(4):977-990. doi: 10.1016/j.celrep.2017.01.003.

Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin.

Author information

1
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, 75185 Uppsala, Sweden.
2
Department of Medical Sciences, Cancer Pharmacology and Computational Medicine, Uppsala University, 75185 Uppsala, Sweden.
3
Department of Forensic Medicine, The National Board of Forensic Medicine, Box 1024, 75140 Uppsala, Sweden.
4
Department of Neuroscience, Uppsala University, Uppsala University Hospital, 75185 Uppsala, Sweden.
5
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, 75185 Uppsala, Sweden. Electronic address: sven.nelander@igp.uu.se.
6
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, 75185 Uppsala, Sweden. Electronic address: lene.uhrbom@igp.uu.se.

Abstract

The identity of the glioblastoma (GBM) cell of origin and its contributions to disease progression and treatment response remain largely unknown. We have analyzed how the phenotypic state of the initially transformed cell affects mouse GBM development and essential GBM cell (GC) properties. We find that GBM induced in neural stem-cell-like glial fibrillary acidic protein (GFAP)-expressing cells in the subventricular zone of adult mice shows accelerated tumor development and produces more malignant GCs (mGC1GFAP) that are less resistant to cancer drugs, compared with those originating from more differentiated nestin- (mGC2NES) or 2,'3'-cyclic nucleotide 3'-phosphodiesterase (mGC3CNP)-expressing cells. Transcriptome analysis of mouse GCs identified a 196 mouse cell origin (MCO) gene signature that was used to partition 61 patient-derived GC lines. Human GC lines that clustered with the mGC1GFAP cells were also significantly more self-renewing, tumorigenic, and sensitive to cancer drugs compared with those that clustered with mouse GCs of more differentiated origin.

KEYWORDS:

cancer stem cell; cell of origin; central nervous system; drug response; glioblastoma; glioma; mouse model; neural stem cell; oligodendrocyte precursor cell; self-renewal

PMID:
28122246
DOI:
10.1016/j.celrep.2017.01.003
[Indexed for MEDLINE]
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