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Fatty acid oxidation is required for the respiration and proliferation of malignant glioma cells.

Elizabeth Stoll, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, U.K.

Glioma is the most common form of primary malignant brain tumour, with ~4 cases per 100,000 people per year. Gliomas, like many tumours, are thought to rely primarily upon aerobic glycolysis for energy production. However, high levels of glycolysis have been identified in brain tumours through the study of cells that have adapted to culture conditions; cells that have been cultured in the absence of serum have been shown to retain their original characteristics and are more suitable for chemical and genetic screening. Our findings demonstrate that primary-cultured human glioma cells grown under serum-free conditions require fatty acid oxidation to maintain respiratory and proliferative activity. Specifically, enzymes required for fatty acid oxidation are observed in cells within human glioblastoma tissue, fatty acid oxidation is the primary contributor to respiratory activity in cells isolated from human glioma, and this metabolic pathway is a limiting factor in the proliferation of human and mouse glioma cells cultured in the absence of serum. Finally, we find that transcriptional upregulation of genes whose products play a role in fatty acid oxidation is significantly associated with lower survival in patients with malignant glioma. Since fatty acid oxidation enzymes are present and functional in glioma tissues, this pathway could potentially be targeted to reduce energy production and cellular proliferation to provide therapeutic benefit to patients with malignant glioma.

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