author_facet 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
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
author 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
spellingShingle 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
Journal of Neurochemistry
Primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity?
Cellular and Molecular Neuroscience
Biochemistry
author_sort lemke, dieter
spelling 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 0022-3042 1471-4159 Wiley Cellular and Molecular Neuroscience Biochemistry http://dx.doi.org/10.1111/jnc.12802 <jats:title>Abstract</jats:title><jats:p>Human glioblastomas may be hierarchically organized. Within this hierarchy, glioblastoma‐initiating cells 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. The protein expression of Nestin and SOX2 as well as the mRNA levels of Musashi1, L1 cell adhesion molecule, CD133, Nestin, and pleiomorphic adenoma gene‐like 2 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, pleiomorphic adenoma gene‐like 2, and CD133 mRNA levels are inversely correlated with radioresistance. Higher expression of stem cell markers does not correlate with resistance to radiochemotherapy in 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. <jats:boxed-text content-type="graphic" position="anchor"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" mimetype="image/png" position="anchor" specific-use="enlarged-web-image" xlink:href="graphic/jnc12802-fig-0007-m.png"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text> </jats:p><jats:p>Markers used to define glioma‐initiating cells (GIC) are generally not defining a more resistant, but rather a more sensitive group of glioma cells. An exemption is CD44 expression. Also proliferation of the GIC culture itself was not systematically associated with radiosensitivity or – resistance, but a SOX‐2 positive, proliferative subgroup within a GIC culture is showing the highest radiosensitivity.</jats:p> Primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity? Journal of Neurochemistry
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series Journal of Neurochemistry
source_id 49
title Primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity?
title_unstemmed Primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity?
title_full Primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity?
title_fullStr Primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity?
title_full_unstemmed Primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity?
title_short Primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity?
title_sort primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity?
topic Cellular and Molecular Neuroscience
Biochemistry
url http://dx.doi.org/10.1111/jnc.12802
publishDate 2014
physical 251-264
description <jats:title>Abstract</jats:title><jats:p>Human glioblastomas may be hierarchically organized. Within this hierarchy, glioblastoma‐initiating cells 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. The protein expression of Nestin and SOX2 as well as the mRNA levels of Musashi1, L1 cell adhesion molecule, CD133, Nestin, and pleiomorphic adenoma gene‐like 2 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, pleiomorphic adenoma gene‐like 2, and CD133 mRNA levels are inversely correlated with radioresistance. Higher expression of stem cell markers does not correlate with resistance to radiochemotherapy in 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. <jats:boxed-text content-type="graphic" position="anchor"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" mimetype="image/png" position="anchor" specific-use="enlarged-web-image" xlink:href="graphic/jnc12802-fig-0007-m.png"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text> </jats:p><jats:p>Markers used to define glioma‐initiating cells (GIC) are generally not defining a more resistant, but rather a more sensitive group of glioma cells. An exemption is CD44 expression. Also proliferation of the GIC culture itself was not systematically associated with radiosensitivity or – resistance, but a SOX‐2 positive, proliferative subgroup within a GIC culture is showing the highest radiosensitivity.</jats:p>
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author 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
author_facet 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, 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
author_sort lemke, dieter
container_issue 2
container_start_page 251
container_title Journal of Neurochemistry
container_volume 131
description <jats:title>Abstract</jats:title><jats:p>Human glioblastomas may be hierarchically organized. Within this hierarchy, glioblastoma‐initiating cells 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. The protein expression of Nestin and SOX2 as well as the mRNA levels of Musashi1, L1 cell adhesion molecule, CD133, Nestin, and pleiomorphic adenoma gene‐like 2 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, pleiomorphic adenoma gene‐like 2, and CD133 mRNA levels are inversely correlated with radioresistance. Higher expression of stem cell markers does not correlate with resistance to radiochemotherapy in 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. <jats:boxed-text content-type="graphic" position="anchor"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" mimetype="image/png" position="anchor" specific-use="enlarged-web-image" xlink:href="graphic/jnc12802-fig-0007-m.png"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text> </jats:p><jats:p>Markers used to define glioma‐initiating cells (GIC) are generally not defining a more resistant, but rather a more sensitive group of glioma cells. An exemption is CD44 expression. Also proliferation of the GIC culture itself was not systematically associated with radiosensitivity or – resistance, but a SOX‐2 positive, proliferative subgroup within a GIC culture is showing the highest radiosensitivity.</jats:p>
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spelling 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 0022-3042 1471-4159 Wiley Cellular and Molecular Neuroscience Biochemistry http://dx.doi.org/10.1111/jnc.12802 <jats:title>Abstract</jats:title><jats:p>Human glioblastomas may be hierarchically organized. Within this hierarchy, glioblastoma‐initiating cells 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. The protein expression of Nestin and SOX2 as well as the mRNA levels of Musashi1, L1 cell adhesion molecule, CD133, Nestin, and pleiomorphic adenoma gene‐like 2 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, pleiomorphic adenoma gene‐like 2, and CD133 mRNA levels are inversely correlated with radioresistance. Higher expression of stem cell markers does not correlate with resistance to radiochemotherapy in 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. <jats:boxed-text content-type="graphic" position="anchor"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" mimetype="image/png" position="anchor" specific-use="enlarged-web-image" xlink:href="graphic/jnc12802-fig-0007-m.png"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text> </jats:p><jats:p>Markers used to define glioma‐initiating cells (GIC) are generally not defining a more resistant, but rather a more sensitive group of glioma cells. An exemption is CD44 expression. Also proliferation of the GIC culture itself was not systematically associated with radiosensitivity or – resistance, but a SOX‐2 positive, proliferative subgroup within a GIC culture is showing the highest radiosensitivity.</jats:p> Primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity? Journal of Neurochemistry
spellingShingle 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, Journal of Neurochemistry, Primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity?, Cellular and Molecular Neuroscience, Biochemistry
title Primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity?
title_full Primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity?
title_fullStr Primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity?
title_full_unstemmed Primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity?
title_short Primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity?
title_sort primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity?
title_unstemmed Primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity?
topic Cellular and Molecular Neuroscience, Biochemistry
url http://dx.doi.org/10.1111/jnc.12802