Radiation-induced PGE₂sustains human glioma cell growth and survival through EGF signaling

// Emeline Brocard 1, 2, * , Kristell Oizel 1, 2, * , Lisenn Lalier 1, 2, 3 , Claire Pecqueur 1, 2 , François Paris 1, 2, 3 , François M. Vallette 1, 2, 3 , Lisa Oliver 1, 2, 4 1 Centre de Recherche en Cancérologie Nantes Angers UMR INSERM 892, CNRS 6299, Université de Nantes, 44007 Nantes, France 2 Université de Nantes, Faculté de Médecine, 44007 Nantes, France 3 LaBCT, Institut de Cancérologie de l'Ouest, 44805 St Herblain cedex, France 4 CHU de Nantes, 1 Place Alexis Ricordeau, 44093 Nantes, France * These authors have contributed equally to this work Correspondence to: Lisa Oliver, e-mail: lisa.oliver@univ-nantes.fr François M. Vallette, e-mail: francois.vallette@inserm.fr Keywords: Radiation, caspase, prostaglandin, glioblastoma, EGFR Received: December 08, 2014      Accepted: January 16, 2014      Published: February 25, 2015 ABSTRACT 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 (PGE 2 ), 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 PGE 2 in important quantities independently of the induction of cell death. We demonstrate that the addition of PGE 2 enhances cell survival and proliferation though its ability to trans-activate the Epithelial Growth Factor receptor (EGFR) and to activate β-catenin. Indeed, PGE 2 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.