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New role of osteopontin in DNA repair and impact on human glioblastoma radiosensitivity

Glioblastoma (GBM) represents the most aggressive and common solid human brain tumor. We have recently demonstrated the importance of osteopontin (OPN) in the acquisition/maintenance of stemness characters and tumorigenicity of glioma initiating cells. Consultation of publicly available TCGA databas...

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Autores principales: Henry, Aurélie, Nokin, Marie-Julie, Leroi, Natacha, Lallemand, François, Lambert, Jérémy, Goffart, Nicolas, Roncarati, Patrick, Bianchi, Elettra, Peixoto, Paul, Blomme, Arnaud, Turtoi, Andrei, Peulen, Olivier, Habraken, Yvette, Scholtes, Félix, Martinive, Philippe, Delvenne, Philippe, Rogister, Bernard, Castronovo, Vincent, Bellahcène, Akeila
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325397/
https://www.ncbi.nlm.nih.gov/pubmed/27563812
http://dx.doi.org/10.18632/oncotarget.11483
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author Henry, Aurélie
Nokin, Marie-Julie
Leroi, Natacha
Lallemand, François
Lambert, Jérémy
Goffart, Nicolas
Roncarati, Patrick
Bianchi, Elettra
Peixoto, Paul
Blomme, Arnaud
Turtoi, Andrei
Peulen, Olivier
Habraken, Yvette
Scholtes, Félix
Martinive, Philippe
Delvenne, Philippe
Rogister, Bernard
Castronovo, Vincent
Bellahcène, Akeila
author_facet Henry, Aurélie
Nokin, Marie-Julie
Leroi, Natacha
Lallemand, François
Lambert, Jérémy
Goffart, Nicolas
Roncarati, Patrick
Bianchi, Elettra
Peixoto, Paul
Blomme, Arnaud
Turtoi, Andrei
Peulen, Olivier
Habraken, Yvette
Scholtes, Félix
Martinive, Philippe
Delvenne, Philippe
Rogister, Bernard
Castronovo, Vincent
Bellahcène, Akeila
author_sort Henry, Aurélie
collection PubMed
description Glioblastoma (GBM) represents the most aggressive and common solid human brain tumor. We have recently demonstrated the importance of osteopontin (OPN) in the acquisition/maintenance of stemness characters and tumorigenicity of glioma initiating cells. Consultation of publicly available TCGA database indicated that high OPN expression correlated with poor survival in GBM patients. In this study, we explored the role of OPN in GBM radioresistance using an OPN-depletion strategy in U87-MG, U87-MG vIII and U251-MG human GBM cell lines. Clonogenic experiments showed that OPN-depleted GBM cells were sensitized to irradiation. In comet assays, these cells displayed higher amounts of unrepaired DNA fragments post-irradiation when compared to control. We next evaluated the phosphorylation of key markers of DNA double-strand break repair pathway. Activating phosphorylation of H2AX, ATM and 53BP1 was significantly decreased in OPN-deficient cells. The addition of recombinant OPN prior to irradiation rescued phospho-H2AX foci formation thus establishing a new link between DNA repair and OPN expression in GBM cells. Finally, OPN knockdown improved mice survival and induced a significant reduction of heterotopic human GBM xenograft when combined with radiotherapy. This study reveals a new function of OPN in DNA damage repair process post-irradiation thus further confirming its major role in GBM aggressive disease.
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spelling pubmed-53253972017-03-23 New role of osteopontin in DNA repair and impact on human glioblastoma radiosensitivity Henry, Aurélie Nokin, Marie-Julie Leroi, Natacha Lallemand, François Lambert, Jérémy Goffart, Nicolas Roncarati, Patrick Bianchi, Elettra Peixoto, Paul Blomme, Arnaud Turtoi, Andrei Peulen, Olivier Habraken, Yvette Scholtes, Félix Martinive, Philippe Delvenne, Philippe Rogister, Bernard Castronovo, Vincent Bellahcène, Akeila Oncotarget Research Paper Glioblastoma (GBM) represents the most aggressive and common solid human brain tumor. We have recently demonstrated the importance of osteopontin (OPN) in the acquisition/maintenance of stemness characters and tumorigenicity of glioma initiating cells. Consultation of publicly available TCGA database indicated that high OPN expression correlated with poor survival in GBM patients. In this study, we explored the role of OPN in GBM radioresistance using an OPN-depletion strategy in U87-MG, U87-MG vIII and U251-MG human GBM cell lines. Clonogenic experiments showed that OPN-depleted GBM cells were sensitized to irradiation. In comet assays, these cells displayed higher amounts of unrepaired DNA fragments post-irradiation when compared to control. We next evaluated the phosphorylation of key markers of DNA double-strand break repair pathway. Activating phosphorylation of H2AX, ATM and 53BP1 was significantly decreased in OPN-deficient cells. The addition of recombinant OPN prior to irradiation rescued phospho-H2AX foci formation thus establishing a new link between DNA repair and OPN expression in GBM cells. Finally, OPN knockdown improved mice survival and induced a significant reduction of heterotopic human GBM xenograft when combined with radiotherapy. This study reveals a new function of OPN in DNA damage repair process post-irradiation thus further confirming its major role in GBM aggressive disease. Impact Journals LLC 2016-08-22 /pmc/articles/PMC5325397/ /pubmed/27563812 http://dx.doi.org/10.18632/oncotarget.11483 Text en Copyright: © 2016 Henry et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Henry, Aurélie
Nokin, Marie-Julie
Leroi, Natacha
Lallemand, François
Lambert, Jérémy
Goffart, Nicolas
Roncarati, Patrick
Bianchi, Elettra
Peixoto, Paul
Blomme, Arnaud
Turtoi, Andrei
Peulen, Olivier
Habraken, Yvette
Scholtes, Félix
Martinive, Philippe
Delvenne, Philippe
Rogister, Bernard
Castronovo, Vincent
Bellahcène, Akeila
New role of osteopontin in DNA repair and impact on human glioblastoma radiosensitivity
title New role of osteopontin in DNA repair and impact on human glioblastoma radiosensitivity
title_full New role of osteopontin in DNA repair and impact on human glioblastoma radiosensitivity
title_fullStr New role of osteopontin in DNA repair and impact on human glioblastoma radiosensitivity
title_full_unstemmed New role of osteopontin in DNA repair and impact on human glioblastoma radiosensitivity
title_short New role of osteopontin in DNA repair and impact on human glioblastoma radiosensitivity
title_sort new role of osteopontin in dna repair and impact on human glioblastoma radiosensitivity
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325397/
https://www.ncbi.nlm.nih.gov/pubmed/27563812
http://dx.doi.org/10.18632/oncotarget.11483
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