| Added by | standudu |
|---|---|
| Group name | EquipeAT |
| Item Type | Journal Article |
| Title | New role of osteopontin in DNA repair and impact on human glioblastoma radiosensitivity |
| Creator | Henry et al. |
| Author | Aurélie Henry |
| Author | Marie-Julie Nokin |
| Author | Natacha Leroi |
| Author | François Lallemand |
| Author | Jérémy Lambert |
| Author | Nicolas Goffart |
| Author | Patrick Roncarati |
| Author | Elettra Bianchi |
| Author | Paul Peixoto |
| Author | Arnaud Blomme |
| Author | Andrei Turtoi |
| Author | Olivier Peulen |
| Author | Yvette Habraken |
| Author | Félix Scholtes |
| Author | Philippe Martinive |
| Author | Philippe Delvenne |
| Author | Bernard Rogister |
| Author | Vincent Castronovo |
| Author | Akeila Bellahcène |
| Abstract | 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. |
| Publication | Oncotarget |
| Volume | 7 |
| Issue | 39 |
| Pages | 63708-63721 |
| Date | Sep 27, 2016 |
| Journal Abbr | Oncotarget |
| Language | eng |
| DOI | 10.18632/oncotarget.11483 |
| ISSN | 1949-2553 |
| Library Catalog | PubMed |
| Extra | PMID: 27563812 PMCID: PMC5325397 |
| Tags | Animals, Brain Neoplasms, Cell Line, Tumor, Comet Assay, DNA Breaks, Double-Stranded, DNA damage repair, DNA Repair, EGFRvIII, Female, Gene Silencing, glioblastoma, Humans, Mice, Mice, Nude, Mice, SCID, Neoplasm Transplantation, original, Osteopontin, Phosphorylation, Radiation Tolerance, radioresistance, Recombinant Proteins, RNA, Small Interfering |
| Date Added | 2019/05/29 - 14:23:14 |
| Date Modified | 2019/05/29 - 14:32:44 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
Institut de Recherche en Cancérologie de
