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A novel stem cell culture model of recurrent glioblastoma

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Abstract

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults with average disease relapse at 9 months and median survival rarely extending beyond 15 months. Brain tumor stem cells (BTSCs) have been implicated in not only initiating GBM but also conferring resistance to therapy. However, it is not clear whether the BTSC population that initiates tumor growth is also responsible for GBM recurrence. In this study, we have developed a novel in vitro treatment model to profile the evolution of primary treatment-naïve GBM BTSCs through chemoradiotherapy. We report that our in vitro model enriched for a CD15+/CD133− BTSC population, mirroring the phenotype of BTSCs in recurrent GBM. We also show that in vitro treatment increased stem cell gene expression as well as self-renewal capacity of primary GBMs. In addition, the chemoradiotherapy-refractory gene signature obtained from gene expression profiling identified a hyper-aggressive subtype of glioma. The delivery of in vitro chemoradiotherapy to primary GBM BTSCs models several aspects of recurrent GBM biology, and could be used as a discovery and drug-screening platform to uncover new biological drivers and therapeutic targets in GBM.

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Authors and Affiliations

  1. McMaster Stem Cell and Cancer Research Institute, McMaster University, MDCL 5027, 1200 Main Street West, Hamilton, ON, L8S 4K1, Canada

    Maleeha A. Qazi, Parvez Vora, Chitra Venugopal, Nicole McFarlane, Minomi K. Subapanditha & Sheila K. Singh

  2. Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4L8, Canada

    Maleeha A. Qazi, Minomi K. Subapanditha, John A. Hassell, Robin M. Hallett & Sheila K. Singh

  3. Department of Surgery, Faculty of Health Sciences, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4L8, Canada

    Parvez Vora, Chitra Venugopal, Nicole McFarlane, Naresh K. Murty & Sheila K. Singh

  4. McMaster Centre for Functional Genomics, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada

    John A. Hassell & Robin M. Hallett

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  1. Maleeha A. Qazi
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Correspondence to Sheila K. Singh.

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Funding

Stem Cell Network Undergraduate Co-op Award and Canadian Institute of Health Research Canada Graduate Scholarship – Master’s Award (to M.A.Q.); Stem Cell Network Stem Cell Drug Discovery Award, Terry Fox Foundation New Investigator Award, Ontario Institute for Cancer Research Cancer Stem Cell Program, and Canada Research Chair Award (to S.K.S.).

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The authors declare no conflict of interests.

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Qazi, M.A., Vora, P., Venugopal, C. et al. A novel stem cell culture model of recurrent glioblastoma. J Neurooncol 126, 57–67 (2016). https://doi.org/10.1007/s11060-015-1951-6

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  • DOI: https://doi.org/10.1007/s11060-015-1951-6

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