Research: RODRÍGUEZ and COLLEAGUES,

Listed in Issue 247

Abstract

RODRÍGUEZ and COLLEAGUES, (1)Laboratory of Neurobiology and Stem Cells, Center for Advanced Microscopy CMA BIOBIO, University of Concepcion, Concepcion, Chile evaluated superoxide-dependent uptake of vitamin C in human glioma cells.

Background

Glioblastomas are lethal brain tumours that resist current cytostatic therapies. Vitamin C may antagonize the effects of reactive oxygen species (ROS) generating therapies; however, it is often used to reduce therapy-related side effects despite its effects on therapy or tumor growth.

Methodology

Because the mechanisms of vitamin C uptake in gliomas are currently unknown, we evaluated the expression of the sodium-vitamin C cotransporter (SVCT) and facilitative hexose transporter (GLUT) families in human glioma cells. In addition, as microglial cells can greatly infiltrate high-grade gliomas (constituting up to 45% of cells in glioblastomas), the effect of TC620 glioma cell interactions with microglial-like HL60 cells on vitamin C uptake (Bystander effect) was determined.

Results

Although glioma cells expressed high levels of the SVCT isoform-2 (SVCT2), low functional activity, intracellular localization and the expression of the dominant-negative isoform (dnSVCT2) were observed. The increased glucose metabolic activity of glioma cells was evident by the high 2-Deoxy-d-glucose and dehydroascorbic acid (DHA) uptake rates through the GLUT isoform-1 (GLUT1), the main DHA transporter in glioblastoma. Co-culture of glioma cells and activated microglial-like HL60 cells resulted in extracellular ascorbic acid oxidation and high DHA uptake by glioma cells. This Bystander effect may explain the high antioxidative potential observed in high-grade gliomas.

Conclusion

This study strongly suggests that the Bystander effect, that is, glioma cell interaction with oxidant-producing microglia, could be an important mechanism for glioma vitamin C loading in the absence of functional sodium-vitamin C cotransporter 2 (SVCT2) expression. The high cellular vitamin C load in glioma cells results from a high uptake of extracellular dehydroascorbic acid (DHA) generated by neighbouring microglia. This Bystander effect may explain the high antioxidative potential observed in high-grade gliomas, considering that high-grade gliomas may be the only neoplasm where oxidant-producing microglia can almost equal the number of tumour cells.

References

Rodríguez FS(1), Salazar KA, Jara NA, García-Robles MA, Pérez F, Ferrada LE, Martínez F, Nualart FJ. Superoxide-dependent uptake of vitamin C in human glioma cells. J Neurochem: 127(6):793-804. Dec 2013. doi: 10.1111/jnc.12365. Epub Aug 19 2013.

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