Glutamine anaplerosis is required for amino acid biosynthesis in human meningiomas.

Amino Acids Child Glutamic Acid / metabolism Glutamine / metabolism Humans Magnetic Resonance Spectroscopy / methods Meningeal Neoplasms / metabolism Meningioma / metabolism
alanine glutamine meningioma metabolic flux analysis metabolomics

Journal

Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420

Informations de publication

Date de publication:
01 04 2022
Historique:
pubmed: 14 9 2021
medline: 5 4 2022
entrez: 13 9 2021
Statut: ppublish

Résumé

We postulate that meningiomas undergo distinct metabolic reprogramming in tumorigenesis and unraveling their metabolic phenotypes provide new therapeutic insights. Glutamine catabolism is key to the growth and proliferation of tumors. Here, we investigated the metabolomics of freshly resected meningiomas and glutamine metabolism in patient-derived meningioma cells. 1H NMR spectroscopy of tumor tissues from meningioma patients was used to differentiate the metabolite profiles of grade-I and grade-II meningiomas. Glutamine metabolism was examined using 13C/15N glutamine tracer, in 5 patient-derived meningioma cells. Alanine, lactate, glutamate, glutamine, and glycine were predominantly elevated only in grade-II meningiomas by 74%, 76%, 35%, 75%, and 33%, respectively, with alanine and glutamine levels being statistically significant (P ≤ .02). 13C/15N glutamine tracer experiments revealed that both grade-I and -II meningiomas actively metabolize glutamine to generate various key carbon intermediates including alanine and proline that are necessary for the tumor growth. Also, it is shown that glutaminase (GLS1) inhibitor, CB-839 is highly effective in downregulating glutamine metabolism and decreasing proliferation in meningioma cells. Alanine and glutamine/glutamate are mainly elevated in grade-II meningiomas. Grade-I meningiomas possess relatively higher glutamine metabolism providing carbon/nitrogen for the biosynthesis of key nonessential amino acids. GLS1 inhibitor (CB-839) is very effective in downregulating glutamine metabolic pathways in grade-I meningiomas leading to decreased cellular proliferation.

Sections du résumé

BACKGROUND
We postulate that meningiomas undergo distinct metabolic reprogramming in tumorigenesis and unraveling their metabolic phenotypes provide new therapeutic insights. Glutamine catabolism is key to the growth and proliferation of tumors. Here, we investigated the metabolomics of freshly resected meningiomas and glutamine metabolism in patient-derived meningioma cells.
METHODS
1H NMR spectroscopy of tumor tissues from meningioma patients was used to differentiate the metabolite profiles of grade-I and grade-II meningiomas. Glutamine metabolism was examined using 13C/15N glutamine tracer, in 5 patient-derived meningioma cells.
RESULTS
Alanine, lactate, glutamate, glutamine, and glycine were predominantly elevated only in grade-II meningiomas by 74%, 76%, 35%, 75%, and 33%, respectively, with alanine and glutamine levels being statistically significant (P ≤ .02). 13C/15N glutamine tracer experiments revealed that both grade-I and -II meningiomas actively metabolize glutamine to generate various key carbon intermediates including alanine and proline that are necessary for the tumor growth. Also, it is shown that glutaminase (GLS1) inhibitor, CB-839 is highly effective in downregulating glutamine metabolism and decreasing proliferation in meningioma cells.
CONCLUSION
Alanine and glutamine/glutamate are mainly elevated in grade-II meningiomas. Grade-I meningiomas possess relatively higher glutamine metabolism providing carbon/nitrogen for the biosynthesis of key nonessential amino acids. GLS1 inhibitor (CB-839) is very effective in downregulating glutamine metabolic pathways in grade-I meningiomas leading to decreased cellular proliferation.

Identifiants

DOI: 10.1093/neuonc/noab219 PMID: 34515312 PMC: PMC8972231
pubmed: 34515312
pii: 6369334
doi: 10.1093/neuonc/noab219
pmc: PMC8972231
doi:

Substances chimiques

Amino Acids 0
Glutamine 0RH81L854J
Glutamic Acid 3KX376GY7L

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

556-568

Commentaires et corrections

Type : CommentIn

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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Auteurs

Omkar B Ijare (OB)

Kenneth R. Peak Brain and Pituitary Tumor Treatment Center, Department of Neurosurgery, Houston Methodist Neurological Institute, Houston Methodist Hospital and Research Institute, Houston, Texas, USA.

Shashank Hambarde (S)

Kenneth R. Peak Brain and Pituitary Tumor Treatment Center, Department of Neurosurgery, Houston Methodist Neurological Institute, Houston Methodist Hospital and Research Institute, Houston, Texas, USA.

Fabio Henrique Brasil da Costa (FH)

Kenneth R. Peak Brain and Pituitary Tumor Treatment Center, Department of Neurosurgery, Houston Methodist Neurological Institute, Houston Methodist Hospital and Research Institute, Houston, Texas, USA.

Sophie Lopez (S)

Kenneth R. Peak Brain and Pituitary Tumor Treatment Center, Department of Neurosurgery, Houston Methodist Neurological Institute, Houston Methodist Hospital and Research Institute, Houston, Texas, USA.

Martyn A Sharpe (MA)

Kenneth R. Peak Brain and Pituitary Tumor Treatment Center, Department of Neurosurgery, Houston Methodist Neurological Institute, Houston Methodist Hospital and Research Institute, Houston, Texas, USA.

Santosh A Helekar (SA)

Kenneth R. Peak Brain and Pituitary Tumor Treatment Center, Department of Neurosurgery, Houston Methodist Neurological Institute, Houston Methodist Hospital and Research Institute, Houston, Texas, USA.
Weill Cornell Medical College, New York, New York, USA.

Gilbert Hangel (G)

High-Field MR Center, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.

Wolfgang Bogner (W)

High-Field MR Center, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.

Georg Widhalm (G)

Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.

Robert M Bachoo (RM)

Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, Texas, USA.

David S Baskin (DS)

Kenneth R. Peak Brain and Pituitary Tumor Treatment Center, Department of Neurosurgery, Houston Methodist Neurological Institute, Houston Methodist Hospital and Research Institute, Houston, Texas, USA.
Weill Cornell Medical College, New York, New York, USA.

Kumar Pichumani (K)

Kenneth R. Peak Brain and Pituitary Tumor Treatment Center, Department of Neurosurgery, Houston Methodist Neurological Institute, Houston Methodist Hospital and Research Institute, Houston, Texas, USA.
Weill Cornell Medical College, New York, New York, USA.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Glutamine anaplerosis is required for amino...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Glutamine anaplerosis is required for amino...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés excitateurs › Acide glutamique › Glutamine anaplerosis is required for amino...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés neutres › Glutamine › Glutamine anaplerosis is required for amino...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Glutamine anaplerosis is required for amino...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Analyse spectrale › Spectroscopie par résonance magnétique › Glutamine anaplerosis is required for amino...
questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs des méninges › Glutamine anaplerosis is required for amino...
questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs des méninges › Méningiome › Glutamine anaplerosis is required for amino...