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Cell. 2014 Dec 18;159(7):1603-14. doi: 10.1016/j.cell.2014.11.025.

Acetate is a bioenergetic substrate for human glioblastoma and brain metastases.

Author information

1
Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA; Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
2
Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX 75390, USA.
3
Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
4
Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
5
Annette G. Strauss Center for Neuro-Oncology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
6
Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
7
Department of Biochemistry, UT Southwestern Medical Center, Dallas, TX 75390, USA.
8
Department of Neurological Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
9
Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neurological Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
10
Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA; McDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, TX 75390, USA; Children's Medical Center Research Institute, UT Southwestern Medical Center, Dallas, TX 75390, USA.
11
Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA; Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: elizabeth.maher@utsouthwestern.edu.
12
Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA; Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA; Annette G. Strauss Center for Neuro-Oncology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: robert.bachoo@utsouthwestern.edu.

Abstract

Glioblastomas and brain metastases are highly proliferative brain tumors with short survival times. Previously, using (13)C-NMR analysis of brain tumors resected from patients during infusion of (13)C-glucose, we demonstrated that there is robust oxidation of glucose in the citric acid cycle, yet glucose contributes less than 50% of the carbons to the acetyl-CoA pool. Here, we show that primary and metastatic mouse orthotopic brain tumors have the capacity to oxidize [1,2-(13)C]acetate and can do so while simultaneously oxidizing [1,6-(13)C]glucose. The tumors do not oxidize [U-(13)C]glutamine. In vivo oxidation of [1,2-(13)C]acetate was validated in brain tumor patients and was correlated with expression of acetyl-CoA synthetase enzyme 2, ACSS2. Together, the data demonstrate a strikingly common metabolic phenotype in diverse brain tumors that includes the ability to oxidize acetate in the citric acid cycle. This adaptation may be important for meeting the high biosynthetic and bioenergetic demands of malignant growth.

PMID:
25525878
PMCID:
PMC4374602
DOI:
10.1016/j.cell.2014.11.025
[Indexed for MEDLINE]
Free PMC Article

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