1. Exp Neurol. 2009 Jul;218(1):56-63. Epub 2009 Apr 15.

Enhanced expression of the high affinity glutamate transporter GLT-1 in C6 glioma
cells delays tumour progression in rat.

Vanhoutte N, Abarca-Quinones J, Jordan BF, Gallez B, Maloteaux JM, Hermans E.

Laboratory of Experimental Pharmacology, Université catholique de Louvain, 54.10,
Av. Hippocrate 54, 1200 Brussels, Belgium.

High grade gliomas are known to release excitotoxic concentrations of glutamate, 
a process thought to contribute to their malignant phenotype through enhanced
autocrine stimulation of their proliferation and destruction of the surrounding
nervous tissue. A model of C6 glioma cells in which expression of the high
affinity glutamate transporter GLT-1 can be manipulated both in vivo and in vitro
was used in order to investigate the consequences of increasing glutamate
clearance on tumour progression. These cells were grafted in the striatum of
Wistar rats and doxycycline was administered after validation of tumour
development by magnetic resonance imaging. Both GLT-1 expression examined by
immunohistochemistry and glutamate transport activity measured on synaptosomes
appeared robustly increased in samples from doxycycline-treated animals.
Moreover, these rats showed extended survival times as compared to
vehicle-treated animals, an effect that was consistent with volumetric data
revealing delayed tumour growth. As constitutive deficiency in glutamate
clearance at the vicinity of brain tumours is well established, these data
illustrate the potential benefit that could be obtained by enhancing glutamate
transport by glioma cells in order to reduce their invasive behaviour.

PMID: 19374901 [PubMed - indexed for MEDLINE]