Metabolic Constants and Plasticity of Cancer Cells in a Limiting Glucose and Glutamine Microenvironment—A Pyruvate Perspective

The metabolism of cancer cells is an issue of dealing with fluctuating and limiting levels of nutrients in a precarious microenvironment to ensure their vitality and propagation. Glucose and glutamine are central metabolites for catabolic and anabolic metabolism, which is in the limelight of numerou...

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Published in:Frontiers in oncology Vol. 10; p. 596197
Main Author: Otto, Angela M.
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 08.12.2020
Subjects:
13C-glucose tracing
anaplerosis
glutamine
glycolysis
nutrient deprivation
Oncology
TCA-cycle
pyruvate replenishment
13C-glucose tracing
TCA-cycle
anaplerosis
nutrient deprivation
glycolysis
glutamine
metabolic network
ISSN:2234-943X, 2234-943X
Online Access:Get full text
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Summary:The metabolism of cancer cells is an issue of dealing with fluctuating and limiting levels of nutrients in a precarious microenvironment to ensure their vitality and propagation. Glucose and glutamine are central metabolites for catabolic and anabolic metabolism, which is in the limelight of numerous diagnostic methods and therapeutic targeting. Understanding tumor metabolism in conditions of nutrient depletion is important for such applications and for interpreting the readouts. To exemplify the metabolic network of tumor cells in a model system, the fate 13 C 6 -glucose was tracked in a breast cancer cell line growing in variable low glucose/low glutamine conditions. 13 C-glucose-derived metabolites allowed to deduce the engagement of metabolic pathways, namely glycolysis, the TCA-cycle including glutamine and pyruvate anaplerosis, amino acid synthesis (serine, glycine, aspartate, glutamate), gluconeogenesis, and pyruvate replenishment. While the metabolic program did not change, limiting glucose and glutamine supply reduced cellular metabolite levels and enhanced pyruvate recycling as well as pyruvate carboxylation for entry into the TCA-cycle. Otherwise, the same metabolic pathways, including gluconeogenesis, were similarly engaged with physiologically saturating as with limiting glucose and glutamine. Therefore, the metabolic plasticity in precarious nutritional microenvironment does not require metabolic reprogramming, but is based on dynamic changes in metabolite quantity, reaction rates, and directions of the existing metabolic network.
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This article was submitted to Cancer Metabolism, a section of the journal Frontiers in Oncology
Reviewed by: Khalid Omer Alfarouk, Alfarouk Biomedical Research LLC, United States; Angela Ostuni, University of Basilicata, Italy
Edited by: Fatima Baltazar, University of Minho, Portugal
ISSN:2234-943X
2234-943X
DOI:10.3389/fonc.2020.596197