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Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin
- Source :
- Cell Reports, Vol 19, Iss 5, Pp 1080-1081 (2017), Cell Reports, Vol 18, Iss 4, Pp 977-990 (2017)
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
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.
- Subjects :
- Male
0301 basic medicine
Cell of origin
Cell
drug response
Mice, SCID
self-renewal
oligodendrocyte precursor cell
Nestin
Mice
neural stem cell
0302 clinical medicine
Mice, Inbred NOD
glioma
Tumor Cells, Cultured
Cell Self Renewal
lcsh:QH301-705.5
media_common
Mice, Knockout
Brain Neoplasms
Clinical Laboratory Medicine
Brain
Cell Differentiation
Middle Aged
Klinisk laboratoriemedicin
medicine.anatomical_structure
Female
2',3'-Cyclic-Nucleotide Phosphodiesterases
Adult
Drug
cancer stem cell
Cell Survival
media_common.quotation_subject
mouse model
Antineoplastic Agents
Biology
Malignancy
Disease-Free Survival
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Glial Fibrillary Acidic Protein
medicine
Animals
Humans
Sensitivity (control systems)
Cyclin-Dependent Kinase Inhibitor p19
Aged
Cell Proliferation
glioblastoma
cell of origin
medicine.disease
central nervous system
030104 developmental biology
lcsh:Biology (General)
Cancer research
Glioblastoma
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 22111247
- Volume :
- 18
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....a5c7d22a8532f7f59331a03668bcaca7
- Full Text :
- https://doi.org/10.1016/j.celrep.2017.01.003