Targeting the erythropoietin receptor on glioma cells reduces tumour growth

Elodie A Pérès; Samuel Valable; Jean-Sébastien Guillamo; Léna Marteau; Jean-François Bernaudin; Simon Roussel; Emmanuèle Lechapt-Zalcman; Myriam Bernaudin; Edwige Petit

doi:10.1016/j.yexcr.2011.06.011

Targeting the erythropoietin receptor on glioma cells reduces tumour growth

Exp Cell Res. 2011 Oct 1;317(16):2321-32. doi: 10.1016/j.yexcr.2011.06.011. Epub 2011 Jun 30.

Authors

Elodie A Pérès¹, Samuel Valable, Jean-Sébastien Guillamo, Léna Marteau, Jean-François Bernaudin, Simon Roussel, Emmanuèle Lechapt-Zalcman, Myriam Bernaudin, Edwige Petit

Affiliation

¹ CERVOxy team Hypoxia and cerebrovascular pathophysiology, UMR 6232 CI-NAPS, Université de Caen Basse-Normandie, Université Paris-Descartes, Caen, France.

PMID: 21749867
DOI: 10.1016/j.yexcr.2011.06.011

Abstract

Hypoxia has been shown to be one of the major events involved in EPO expression. Accordingly, EPO might be expressed by cerebral neoplastic cells, especially in glioblastoma, known to be highly hypoxic tumours. The expression of EPOR has been described in glioma cells. However, data from the literature remain descriptive and controversial. On the basis of an endogenous source of EPO in the brain, we have focused on a potential role of EPOR in brain tumour growth. In the present study, with complementary approaches to target EPO/EPOR signalling, we demonstrate the presence of a functional EPO/EPOR system on glioma cells leading to the activation of the ERK pathway. This EPO/EPOR system is involved in glioma cell proliferation in vitro. In vivo, we show that the down-regulation of EPOR expression on glioma cells reduces tumour growth and enhances animal survival. Our results support the hypothesis that EPOR signalling in tumour cells is involved in the control of glioma growth.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Astrocytes / metabolism
Brain Neoplasms / drug therapy*
Brain Neoplasms / metabolism
Brain Neoplasms / pathology*
Caudate Nucleus / pathology
Cell Hypoxia / physiology
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Culture Media, Conditioned / pharmacology
Erythropoietin / antagonists & inhibitors
Erythropoietin / genetics
Erythropoietin / metabolism
Erythropoietin / pharmacology
Extracellular Signal-Regulated MAP Kinases / metabolism
Gene Expression / genetics
Glioma / drug therapy*
Glioma / metabolism
Glioma / pathology
Hep G2 Cells
Humans
MAP Kinase Signaling System / physiology
Male
Mice
Mice, Nude
Phosphorylation / drug effects
RNA, Small Interfering / genetics
RNA, Small Interfering / pharmacology
RNA, Small Interfering / therapeutic use
Rats
Rats, Inbred F344
Receptors, Erythropoietin / antagonists & inhibitors*
Receptors, Erythropoietin / genetics
Receptors, Erythropoietin / metabolism
Sequence Deletion / physiology
Signal Transduction / drug effects
Signal Transduction / physiology*
Survival Analysis
Xenograft Model Antitumor Assays

Substances

Culture Media, Conditioned
EPO protein, human
RNA, Small Interfering
Receptors, Erythropoietin
Erythropoietin
Extracellular Signal-Regulated MAP Kinases