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

Lookup NU author(s): Hua Lin, Waseema Patel, Val Affleck, Professor Doug Turnbull, Abhishek Joshi, Dr Ross Maxwell, Dr Elizabeth Stoll

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


Abstract

Background. Glioma is the most common form of primary malignant brain tumor in adults, with approximately 4 cases per100 000 people each year. Gliomas, like many tumors, are thought to primarily metabolize glucose for energy production; however,the reliance upon glycolysis has recently been called into question. In this study, we aimed to identify the metabolic fuelrequirements of human glioma cells.Methods. We used database searches and tissue culture resources to evaluate genotype and protein expression, tracked oxygenconsumption rates to study metabolic responses to various substrates, performed histochemical techniques and fluorescenceactivatedcell sorting-based mitotic profiling to study cellular proliferation rates, and employed an animal model of malignantglioma to evaluate a new therapeutic intervention.Results. We observed the presence of enzymes required for fatty acid oxidation within human glioma tissues. In addition, wedemonstrated that this metabolic pathway is a major contributor to aerobic respiration in primary-cultured cells isolated fromhuman glioma and grown under serum-free conditions. Moreover, inhibiting fatty acid oxidation reduces proliferative activity inthese primary-cultured cells and prolongs survival in a syngeneic mouse model of malignant glioma.Conclusions. Fatty acid oxidation enzymes are present and active within glioma tissues. Targeting this metabolic pathway reducesenergy production and cellular proliferation in glioma cells. The drug etomoxir may provide therapeutic benefit to patients withmalignant glioma. In addition, the expression of fatty acid oxidation enzymes may provide prognostic indicators for clinicalpractice.


Publication metadata

Author(s): Lin H, Patel S, Affleck VS, Wilson I, Turnbull DM, Joshi AR, Maxwell R, Stoll EA

Publication type: Article

Publication status: Published

Journal: Neuro-Oncology

Year: 2017

Volume: 19

Issue: 1

Pages: 43-54

Print publication date: 01/01/2017

Online publication date: 29/06/2016

Acceptance date: 11/05/2016

ISSN (print): 1522-8517

ISSN (electronic): 1523-5866

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/neuonc/now128

DOI: 10.1093/neuonc/now128


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