Glial cell-line derived neurotrophic factor (GDNF) family of ligands confer chemoresistance in a ligand-specific fashion in malignant gliomas

Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia
Wai Hoe NgHeng Phon Too

Abstract

Glial cell-line derived neurotrophic factor (GDNF) is a neurotrophic factor known to promote neuronal survival of dopaminergic neurons in the embryonic midbrain as well as contribute to carcinogenesis in many cancers. Its ubiquitous presence in the central nervous system suggests a role in the mitogenesis of high-grade astrocytoma. GDNF is overexpressed in glioblastoma cell lines and human gliomas. GFRalpha1b is the predominant spliced receptor isoform in human gliomas and RET9 is the predominant co-receptor. Significantly there is differential overexpression of the GFRalpha1b spliced isoform compared to the GFRalpha1a spliced variant. Pre-treatment of glioblastoma cell lines with GDNF but not the alternative ligand neurturin, promoted mitogenic behaviour and conferred chemoresistance to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Signaling mapping of BCNU and GDNF suggest that the ability of GDNF to promote Akt activity and inhibit JNK activity may contribute to the increased cellular survival after BCNU chemotherapy.

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Citations

Dec 3, 2013·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Duncun Xun Kiat HoWai Hoe Ng
Nov 3, 2010·Virus Research·Liliana Soroceanu, Charles S Cobbs
Dec 10, 2014·International Journal of Cancer. Journal International Du Cancer·Ayelet Shabtay-OrbachZiv Gil
Feb 7, 2015·Cell Biology and Toxicology·Jing DingBao-Guo Xiao
Dec 3, 2014·Cell Biochemistry and Biophysics·Jianjun DingQianxue Chen
Jun 28, 2016·Scientific Reports·Marina MorigiGiuseppe Remuzzi

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