Targeting the erythropoietin receptor on glioma cells reduces tumour growth.

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.

• Authors: Elodie A Pérès, Samuel Valable, Jean-Sébastien Guillamo, Léna Marteau, Jean-François Bernaudin, Simon Roussel, Emmanuèle Lechapt-Zalcman, Myriam Bernaudin, Edwige Petit
• Journal: Experimental cell research (Exp Cell Res) Vol. 317 Issue 16 Pg. 2321-32 (Oct 01 2011) ISSN: 1090-2422 [Electronic] United States
• PMID: 21749867 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

• Animals
• Astrocytes (metabolism)
• Brain Neoplasms (drug therapy, metabolism, 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, genetics, metabolism, pharmacology)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Gene Expression (genetics)
• Glioma (drug therapy, metabolism, pathology)
• Hep G2 Cells
• Humans
• MAP Kinase Signaling System (physiology)
• Male
• Mice
• Mice, Nude
• Phosphorylation (drug effects)
• RNA, Small Interfering (genetics, pharmacology, therapeutic use)
• Rats
• Rats, Inbred F344
• Receptors, Erythropoietin (antagonists & inhibitors, genetics, metabolism)
• Sequence Deletion (physiology)
• Signal Transduction (drug effects, physiology)
• Survival Analysis
• Xenograft Model Antitumor Assays