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, N., & Hermans, E. (2008). Glutamate-induced glioma cell proliferation is prevented by functional expression of the glutamate transporter GLT-1. FEBS Letters, 582(13), 1847-1852. https://doi.org/10.1016/j.febslet.2008.04.053 (Original work published 2008)