Oncotarget

Research Papers:

Radiation-induced PGE2 sustains human glioma cell growth and survival through EGF signaling

Emeline Brocard, Kristell Oizel, Lisenn Lalier, Claire Pecqueur, François Paris, François M. Vallette and Lisa Oliver _

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Oncotarget. 2015; 6:6840-6849. https://doi.org/10.18632/oncotarget.3160

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Abstract

Emeline Brocard1,2,*, Kristell Oizel1,2,*, Lisenn Lalier1,2,3, Claire Pecqueur1,2, François Paris1,2,3, François M. Vallette1,2,3, Lisa Oliver1,2,4

1Centre de Recherche en Cancérologie Nantes Angers UMR INSERM 892, CNRS 6299, Université de Nantes, 44007 Nantes, France

2Université de Nantes, Faculté de Médecine, 44007 Nantes, France

3LaBCT, Institut de Cancérologie de l'Ouest, 44805 St Herblain cedex, France

4CHU de Nantes, 1 Place Alexis Ricordeau, 44093 Nantes, France

*These authors have contributed equally to this work

Correspondence to:

Lisa Oliver, e-mail: [email protected]

François M. Vallette, e-mail: [email protected]

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 (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.


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