Reference : Osteopontin as a new target in glioblastoma progression and resistance to radiotherapy
Scientific congresses and symposiums : Unpublished conference/Abstract
Life sciences : Biotechnology
http://hdl.handle.net/2268/186740
Osteopontin as a new target in glioblastoma progression and resistance to radiotherapy
English
[en] L'ostéopontine comme nouvelle cible dans la progression et la radiorésistance du glioblastome
Henry, Aurélie mailto [Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Bellahcene, Akeila mailto [Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Castronovo, Vincenzo mailto [Université de Liège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire >]
Peixoto, Paul mailto [Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Goffart, Nicolas mailto [Université de Liège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine >]
Lallemand, François mailto [Université de Liège > Département des sciences cliniques > Radiothérapie >]
Leroi, Natacha mailto [Université de Liège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire >]
Peulen, Olivier mailto [Université de Liège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques >]
MARTINIVE, Philippe mailto [Centre Hospitalier Universitaire de Liège - CHU > > Service médical de radiothérapie >]
Habraken, Yvette mailto [Université de Liège > > GIGA-R : Virologie - Immunologie >]
Turtoi, Andrei mailto [Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Rogister, Bernard mailto [Université de Liège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine >]
Blomme, Arnaud mailto [> >]
10-Sep-2015
No
International
II International Symposium on clinical and basic investigation in glioblastoma
du 9 septembre au 12 septembre 2015
Université de Castilla la Mancha
Toledo
Espagne
[en] glioblastome ; radiorésistance ; ostéopontine
[en] 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 (TMZ). However, the prognosis of adult patients with GBM remains poor and the survival outcome after treatment does not exceed 15 months. Glioblastoma-composing cells have developed many strategies to counteract these current therapies. Among the wide hallmarks acquired to survive, osteopontin (OPN) ranks correlates with lower overall and disease-free/relapse-free survival in all tumors combined, as well in brain cancer. OPN expression is largely considered as a molecular cancer marker associated with poor prognosis for patients with cancer.
Our preliminary works (Lamour V and Henry A, IJC 2015) have demonstrated the role of OPN in the tumorigenicity of glioblastoma cells and its importance in the maintenance of the stem charachters. Within the continuance of this work, our recent studies focused on the potential role of OPN in the resistance of glioblastoma cells to radiotherapy and its implication in the initiation of Double Strand Breaks (DSBs) repair mechanism.
In this context, U251-MG and U87-MG cells were used to assess the role of OPN in the initiation of the DSBs repair mechanism after an exposure to gamma-irradiation (γ–IR). The transient transfection of both cell lines with siRNA directed against OPN shown a lower induction of γ–H2AX compared to control (irrelevant siRNA). The survival of U251-OPN depleted cells was also affected after an exposure to γ–IR (based on clonogenic assays). However, the sole depletion of OPN in U87 cells affected their survival (independently of the γ–IR). To prove that the secreted form of OPN is necessary to survive after γ–IR, conditionned medium of U87-shSCR clones (rich in OPN) was used to treat U87shOPN clones before an exposure to γ–IR. By immunofluorescence, we observed that the γ–H2AX staining was higher in U87 shOPN clones than when treated with their own conditionned medium (poor in OPN).
Currently, we are investigating the in vivo implication of OPN in the initiation of DSBs repair mechanism after an exposure of mice to γ–IR (whole brain exposure). For this purpose, IPTG-inducible U87 shRNA clones (SCR and OPN) have been generated and validated for an orthotopic xenograft model in NOD-SCID mice. The survival after a radiotherapy of 10 Gy (2Gy per day for 5 days) will be assessed in OPN-positive and –negative tumor-bearing mice.
Taken together, these datas suggest that OPN could represent an important pronostic factor for patient response to radiotherapy in the context of GBM.
Laboratoire de recherche sur les métastases
FNRS - Télévie
osteopontin in glioblastoma radioresistance
Researchers ; Professionals
http://hdl.handle.net/2268/186740

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