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Primary Glioblastoma Cultures: Can Profiling of Stem Cell Markers Predict Radiotherapy Sensitivity?


Lemke, Dieter; Weiler, Markus; Blaes, Jonas; Wiestler, Benedikt; Jestaedt, Leonie; Klein, Ann-Catherine; Löw, Sarah; Eisele, Günter; Radlwimmer, Bernhard; Capper, David; Schmieder, Kirsten; Mittelbronn, Michel; Combs, Stephanie E; Bendszus, Martin; Weller, Michael; Platten, Michael; Wick, Wolfgang (2014). Primary Glioblastoma Cultures: Can Profiling of Stem Cell Markers Predict Radiotherapy Sensitivity? Journal of Neurochemistry, 131(2):251-264.

Abstract

Human glioblastomas may be hierarchically organized. Within this hierarchy, glioblastoma-initiating cells (GIC) have been proposed to be more resistant to radiochemotherapy and responsible for recurrence. Here, established stem cell markers and stem cell attributed characteristics such as self-renewal capacity and tumorigenicity have been profiled in primary glioblastoma cultures to predict radiosensitivity. Furthermore, the sensitivity to radiotherapy of different subpopulations within a single primary glioblastoma culture was analyzed by a flow cytometric approach using Nestin, SRY (sex determining region Y)-box 2 (SOX2) and glial fibrillary acidic protein (GFAP). The protein expression of Nestin and SOX2 as well as the mRNA levels of Musashi1, L1CAM, CD133, Nestin and PLAGL2 inversely correlated with radioresistance in regard to the clonogenic potential. Only CD44 protein expression correlated positively with radioresistance. In terms of proliferation, Nestin protein expression and Musashi1, PLAGL2 and CD133 mRNA levels inversely correlated with radioresistance. Higher expression of stem cell markers does not correlate with resistance to radiochemotherapy in a TCGA (the cancer genome atlas) glioblastoma collective. SOX2 expressing subpopulations exist within single primary glioblastoma cultures. These subpopulations predominantly form the proliferative pool of the primary cultures and are sensitive to irradiation. Thus, profiling of established stem cell markers revealed a surprising result. Except CD44, the tested stem cell markers showed an inverse correlation between expression and radioresistance. This article is protected by copyright. All rights reserved.

Abstract

Human glioblastomas may be hierarchically organized. Within this hierarchy, glioblastoma-initiating cells (GIC) have been proposed to be more resistant to radiochemotherapy and responsible for recurrence. Here, established stem cell markers and stem cell attributed characteristics such as self-renewal capacity and tumorigenicity have been profiled in primary glioblastoma cultures to predict radiosensitivity. Furthermore, the sensitivity to radiotherapy of different subpopulations within a single primary glioblastoma culture was analyzed by a flow cytometric approach using Nestin, SRY (sex determining region Y)-box 2 (SOX2) and glial fibrillary acidic protein (GFAP). The protein expression of Nestin and SOX2 as well as the mRNA levels of Musashi1, L1CAM, CD133, Nestin and PLAGL2 inversely correlated with radioresistance in regard to the clonogenic potential. Only CD44 protein expression correlated positively with radioresistance. In terms of proliferation, Nestin protein expression and Musashi1, PLAGL2 and CD133 mRNA levels inversely correlated with radioresistance. Higher expression of stem cell markers does not correlate with resistance to radiochemotherapy in a TCGA (the cancer genome atlas) glioblastoma collective. SOX2 expressing subpopulations exist within single primary glioblastoma cultures. These subpopulations predominantly form the proliferative pool of the primary cultures and are sensitive to irradiation. Thus, profiling of established stem cell markers revealed a surprising result. Except CD44, the tested stem cell markers showed an inverse correlation between expression and radioresistance. This article is protected by copyright. All rights reserved.

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4 citations in Web of Science®
6 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2014
Deposited On:02 Jul 2014 16:09
Last Modified:05 Apr 2016 17:56
Publisher:Wiley-Blackwell
ISSN:0022-3042
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1111/jnc.12802
PubMed ID:24976529

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