Unpublished conference/Abstract (Scientific congresses and symposiums)
Osteopontin predicts radiotherapy response of glioblastoma patients : new role in DNA damage repair
Henry, Aurélie; Nokin, Marie-Julie; Leroi, Natacha et al.
20163rd Symposium on small animal precision image-guided radiotherapy
 

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Keywords :
Glioblastoma; Radiotherapy; osteopontin
Abstract :
[en] - Introduction: Glioblastoma (GBM) is the most aggressive and common solid human brain tumor. Because of GBM heterogeneity, location and aggressiveness, none of the available treatment is curative. These treatments include maximal surgical resection, radiotherapy and concomitant or adjuvant chemotherapy with Temozolomide. However, the prognosis of adult patients with GBM remains poor and the survival outcome after treatment does not exceed 15 months. GBM-composing cells have developed many strategies to counteract these current therapies. Among the wide hallmarks acquired to survive, high osteopontin (OPN) expression correlates with lower overall and disease-free/relapse-free survival in all tumors combined, as well in brain cancer. Our recent study (Lamour V and Henry A, IJC 2015) has demonstrated the role of OPN in the tumorigenicity of glioblastoma cells and its importance in the maintenance of the stem characters. In the continuation of this work, our recent studies focused on the potential role of OPN in the resistance of GBM cells to radiotherapy and its potential implication in the initiation of Double Strand Breaks (DSBs) repair mechanisms. - Aims: In the context of this study, different GBM cell lines (U251-MG, U87-MG and U87 Viii) were used to assess the role of OPN in the initiation of the DSBs repair mechanism after an exposure to gamma-irradiation. - Methods and results: We performed the transient transfection of different GBM cell lines (U251-MG, U87-MG and U87-MG overexpressing EGFR VIII) with siRNAs specifically directed against OPN. After irradiation, all these OPN-depleted cells consistently showed a lower induction of γ–H2AX compared to control (irrelevant siRNA) as evidenced by western blot and immunofluorescence techniques. Thereafter, clonogenic assays allowed to prove that the survival of OPN-depleted cells was affected after an exposure to irradiation. To assess the importance of OPN expression in the response to radiotherapy, an heterotopic xenograft model was used. In brief, IPTG-inducible U87 shOPN clones were injected subcutaneously in NOD-SCID mice and were allowed to form a tumor. When average tumor volume reached a predetermined size range, mice were treated (or not) with IPTG by intraperitoneal injection during five days. At the end of the treatment, tumors were selectively exposed to gamma-irradiation by using a small animal irradiator X-RAD 225Cx (Precision X-Ray Inc., North Branford, CT). One week later, mice were sacrificed and tumors were measured. In this pilot study, we observed that mice in which the tumor was depleted in OPN displayed a slight regression in the tumor growth compared to mice that received radiotherapy alone (no IPTG), where the tumor volume remained constant. - Conclusions: Taken together, these preliminary data meet the fact that OPN is important in the response of GBM to radiotherapy. The in vitro results converge to the fact that OPN might be implicated in the initiation of the DSBs repair following irradiation. Currently, we would like to investigate this hypothesis in vivo but also to check the effect of OPN depletion combined to radiotherapy on the survival of mice in an orthotopic xenograft model.
Disciplines :
Oncology
Author, co-author :
Henry, Aurélie ;  Université de Liège - ULiège > Form. doc. sc. bioméd. & pharma.
Nokin, Marie-Julie  
Leroi, Natacha ;  Université de Liège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
LALLEMAND, François  ;  Centre Hospitalier Universitaire de Liège - CHU > Radiothérapie
Lambert, Jérémy ;  Université de Liège - ULiège > Form. doc. sc. bioméd. & pharma.
Goffart, Nicolas ;  Université de Liège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine
Peixoto, Paul 
Blomme, Arnaud  
BIANCHI, Elettra ;  Centre Hospitalier Universitaire de Liège - CHU > Service d'anatomie et cytologie pathologiques
Habraken, Yvette ;  Université de Liège > GIGA-R : Virologie - Immunologie
RONCARATI, Patrick ;  Centre Hospitalier Universitaire de Liège - CHU > Service d'anatomie et cytologie pathologiques
Peulen, Olivier  ;  Université de Liège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
SCHOLTES, Félix  ;  Centre Hospitalier Universitaire de Liège - CHU > Service de neurochirurgie
MARTINIVE, Philippe ;  Centre Hospitalier Universitaire de Liège - CHU > Service médical de radiothérapie
Rogister, Bernard  ;  Université de Liège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine
Delvenne, Philippe ;  Université de Liège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Turtoi, Andrei ;  Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Castronovo, Vincenzo ;  Université de Liège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Bellahcene, Akeila  ;  Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
More authors (9 more) Less
Language :
English
Title :
Osteopontin predicts radiotherapy response of glioblastoma patients : new role in DNA damage repair
Alternative titles :
[en] L'ostéopontine comme facteur prédictif dans la réponse des patients atteints d'un glioblastome à la radiothérapie : nouveau rôle dans la réparation de l'ADN
Publication date :
22 March 2016
Event name :
3rd Symposium on small animal precision image-guided radiotherapy
Event organizer :
Frank Verhaegen, Christian Vanhove
Event place :
Gand, Belgium
Event date :
du 21 au 23 mars 2016
Audience :
International
Available on ORBi :
since 19 April 2016

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