Radiation-induced PGE2 sustains human glioma cells growth and survival through EGF signaling.
Glioblastoma Multiforme (GBM) is the most common brain cancer in adults. Radiotherapy (RT) is the most effective post-operative treatment for the patients even though GBM is one of the most radio-resistant tumors. Dead or dying cells within the tumor are thought to promote resistance to treatment through mechanisms that are very poorly understood. We have evaluated the role of Prostaglandin E2 (PGE2), a versatile bioactive lipid, in GBM radio-resistance. We used an in vitro approach using 3D primary cultures derived from representative GBM patients. We show that irradiated glioma cells produced and released PGE2 in important quantities independently of the induction of cell death. We demonstrate that the addition of PGE2 enhances cell survival and proliferation though its ability to trans-activate the Epithelial Growth Factor receptor (EGFR) and to activate β-catenin. Indeed, PGE2 can substitute for EGF to promote primary cultures survival and growth in vitro and the effect is likely to occur though the Prostaglandin E2 receptor EP2.
Centre de Recherche en Cancérologie Nantes Angers UMR INSERM 892, CNRS 6299, Université de Nantes, 44007 Nantes, France.|Université de Nantes, Faculté de Médecine, 44007 Nantes, France.
Emeline
E
Brocard
Centre de Recherche en Cancérologie Nantes Angers UMR INSERM 892, CNRS 6299, Université de Nantes, 44007 Nantes, France.|Université de Nantes, Faculté de Médecine, 44007 Nantes, France.
Kristell
K
Oizel
Centre de Recherche en Cancérologie Nantes Angers UMR INSERM 892, CNRS 6299, Université de Nantes, 44007 Nantes, France.|Université de Nantes, Faculté de Médecine, 44007 Nantes, France.|LaBCT, Institut de Cancérologie de l'Ouest, 44805 St Herblain cedex, France.
Lisenn
L
Lalier
Centre de Recherche en Cancérologie Nantes Angers UMR INSERM 892, CNRS 6299, Université de Nantes, 44007 Nantes, France.|Université de Nantes, Faculté de Médecine, 44007 Nantes, France.
Claire
C
Pecqueur
Centre de Recherche en Cancérologie Nantes Angers UMR INSERM 892, CNRS 6299, Université de Nantes, 44007 Nantes, France.|Université de Nantes, Faculté de Médecine, 44007 Nantes, France.|LaBCT, Institut de Cancérologie de l'Ouest, 44805 St Herblain cedex, France.
François
F
Paris
Centre de Recherche en Cancérologie Nantes Angers UMR INSERM 892, CNRS 6299, Université de Nantes, 44007 Nantes, France.|Université de Nantes, Faculté de Médecine, 44007 Nantes, France.|LaBCT, Institut de Cancérologie de l'Ouest, 44805 St Herblain cedex, France.
François M
FM
Vallette
Centre de Recherche en Cancérologie Nantes Angers UMR INSERM 892, CNRS 6299, Université de Nantes, 44007 Nantes, France.|Université de Nantes, Faculté de Médecine, 44007 Nantes, France.|CHU de Nantes, 44093 Nantes, France.
Lisa
L
Oliver
D017209:Apoptosis; D001932:Brain Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D015232:Dinoprostone / Q000235:genetics*; D066255:EGF Family of Proteins / Q000378:metabolism*; D005909:Glioblastoma / Q000378:metabolism* / Q000532:radiotherapy; D006801:Humans; D008055:Lipids / Q000737:chemistry; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
C495270:CTNNB1 protein, human; D066255:EGF Family of Proteins; D008055:Lipids; D058307:Receptors, Prostaglandin E, EP2 Subtype; D051176:beta Catenin; C505407:CASP3 protein, human; D053148:Caspase 3; D015232:Dinoprostone
EGFR; caspase; glioblastoma; prostaglandin; radiation