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

Publication date: 24 January 2017
Source:Cell Reports, Volume 18, Issue 4
Author(s): Yiwen Jiang, Voichita Dana Marinescu, Yuan Xie, Malin Jarvius, Naga Prathyusha Maturi, Caroline Haglund, Sara Olofsson, Nanna Lindberg, Tommie Olofsson, Caroline Leijonmarck, Göran Hesselager, Irina Alafuzoff, Mårten Fryknäs, Rolf Larsson, Sven Nelander, Lene Uhrbom
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.

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Teaser

The contribution of the glioblastoma cell of origin for disease progression and treatment response remains unclear. Jiang et al. find that the originating cell type affects mouse glioblastoma tumorigenicity and drug sensitivity and validate this using transcriptome and functional analyses on a large panel of human glioblastoma cell lines.


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