Glutamate-induced glioma cell proliferation is prevented by functional expression of the glutamate transporter GLT-1.
A tetracycline-dependent inducible system was used to achieve controlled expression of the glutamate transporter 1 (GLT-1) in C6 glioma cells. Non-induced cells show modest glutamate uptake and, in the presence of L-cystine, these cells tend to release substantial amounts of glutamate. Overnight exposure to doxycycline increased D-[3H]-aspartate uptake, reaching similar capacity as observed in cultured astrocytes. Efficient clearance of exogenously applied glutamate was evidenced in these cells, even in the presence of l-cystine. The addition of glutamate (100 microM) to the medium of non-induced cells significantly increased their proliferation rate, an effect that was blocked when the expression of GLT-1 was induced. This suggests that impaired glutamate uptake capacity in glioma cells indirectly contributes to their proliferation.
Vanhoutte
Nicolas
N
Laboratoire de Pharmacologie Expérimentale, Université catholique de Louvain, 54.10, Av. Hippocrate 54, 1200 Brussels, Belgium.
Hermans
Emmanuel
E
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D014162:Transfection
D027342:Excitatory Amino Acid Transporter 2; D018698:Glutamic Acid