Next Article in Journal
Neuroprotective Effects of Platonin, a Therapeutic Immunomodulating Medicine, on Traumatic Brain Injury in Mice after Controlled Cortical Impact
Next Article in Special Issue
d-Amino Acids Are Exuded by Arabidopsis thaliana Roots to the Rhizosphere
Previous Article in Journal
Hedgehog Signals Mediate Anti-Cancer Drug Resistance in Three-Dimensional Primary Colorectal Cancer Organoid Culture
Previous Article in Special Issue
Branched Chain Amino Acids: Beyond Nutrition Metabolism
Open AccessArticle

Oligodendroglioma Cells Lack Glutamine Synthetase and Are Auxotrophic for Glutamine, but Do not Depend on Glutamine Anaplerosis for Growth

1
Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, Via Volturno 39, 43125 Parma, Italy
2
Laboratory of Industrial Toxicology, Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, Italy
3
Laboratory of Medical Microbiology and Virology, Department of Medicine and Surgery, University of Parma, Via Volturno 39, 43125 Parma, Italy
4
Laboratory of Anatomical Pathology, Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, Italy
5
Cancer Research UK Beatson Institute, Garscube Estate, Switchback road, Glasgow G611BD, UK
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(4), 1099; https://doi.org/10.3390/ijms19041099
Received: 7 March 2018 / Revised: 29 March 2018 / Accepted: 4 April 2018 / Published: 6 April 2018
(This article belongs to the Special Issue Amino Acids Transport and Metabolism)
In cells derived from several types of cancer, a transcriptional program drives high consumption of glutamine (Gln), which is used for anaplerosis, leading to a metabolic addiction for the amino acid. Low or absent expression of Glutamine Synthetase (GS), the only enzyme that catalyzes de novo Gln synthesis, has been considered a marker of Gln-addicted cancers. In this study, two human cell lines derived from brain tumors with oligodendroglioma features, HOG and Hs683, have been shown to be GS-negative. Viability of both lines depends from extracellular Gln with EC50 of 0.175 ± 0.056 mM (Hs683) and 0.086 ± 0.043 mM (HOG), thus suggesting that small amounts of extracellular Gln are sufficient for OD cell growth. Gln starvation does not significantly affect the cell content of anaplerotic substrates, which, consistently, are not able to rescue cell growth, but causes hindrance of the Wnt/β-catenin pathway and protein synthesis attenuation, which is mitigated by transient GS expression. Gln transport inhibitors cause partial depletion of intracellular Gln and cell growth inhibition, but do not lower cell viability. Therefore, GS-negative human oligodendroglioma cells are Gln-auxotrophic but do not use the amino acid for anaplerosis and, hence, are not Gln addicted, exhibiting only limited Gln requirements for survival and growth. View Full-Text
Keywords: anaplerosis; beta-catenin; glutamine; glutamine addiction; glutamine transport; oligodendroglioma anaplerosis; beta-catenin; glutamine; glutamine addiction; glutamine transport; oligodendroglioma
Show Figures

Figure 1

MDPI and ACS Style

Chiu, M.; Taurino, G.; Bianchi, M.G.; Ottaviani, L.; Andreoli, R.; Ciociola, T.; Lagrasta, C.A.M.; Tardito, S.; Bussolati, O. Oligodendroglioma Cells Lack Glutamine Synthetase and Are Auxotrophic for Glutamine, but Do not Depend on Glutamine Anaplerosis for Growth. Int. J. Mol. Sci. 2018, 19, 1099.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map

1
Back to TopTop