Glycolytic Oscillations in Cancer Cells

Amemiya, Takashi; Shibata, Kenichi; Watanabe, Masatoshi; Nakata, Satoshi; Nakamura, Kazuyuki; Yamaguchi, Tomohiko

doi:10.1007/978-3-030-59805-1_15

Cited by 3 publications

(12 citation statements)

References 65 publications

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“…Breast cancer cell spheroids also exhibit increased resistance to antitumor compounds compared with monolayer cells [51]. Thus, our results support our hypothesis that more malignant cancer cells tend to exhibit glycolytic oscillations with higher frequencies than less malignant cells [12], although the availability of glucose for cancer cells should be considered as well.…”

Section: Discussionsupporting

confidence: 87%

“…Glycolytic oscillations in the concentrations of metabolites in the glycolytic pathway have been reported in several cell types including yeast cells [1][2][3][4][5][6], pancreatic β-cells [7,8], ventricular myocytes [9], and cancer cells [10][11][12]. Many studies of glycolytic oscillations have been carried out using cell suspension systems [1] and have revealed collective behaviours in cell populations [13].…”

Section: Introductionmentioning

confidence: 99%

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Glycolytic oscillations in HeLa cervical cancer cell spheroids

et al. 2022

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Previous studies have unravelled glycolytic oscillations in cancer cells, such as HeLa cervical and DU145 prostate cancer cells, using a monolayer culture system. Here, we demonstrate glycolytic oscillations in HeLa cervical cancer cell spheroids. Experiments revealed that a small number of HeLa cells in spheroids exhibited heterogeneous oscillations with a higher frequency than those in monolayers. Model analyses and our previous experiments indicated that the higher frequencies of oscillations in spheroids were mostly due to the increase in glycolytic enzyme activity in the cells, and to the decrease in glucose concentration by diffusional transport of glucose from the surface to inside the spheroids, as well as the increase in cell density through spheroid formation. These results and our previous studies imply that more malignant cancer cells tend to exhibit glycolytic oscillations with higher frequencies than less malignant cells. Adjacent cells in spheroids oscillated within a 10% difference in frequency, but did not synchronize with each other. This suggests that weak cell‐to‐cell interactions might exist among HeLa cells connected with cadherins in the spheroid microenvironment; however, the interactions were not strong enough to induce synchronization of glycolytic oscillations.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Glycolytic oscillations in HeLa cervical cancer cell spheroids

et al. 2022

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“…On the other hand, their amplitudes of NADH fluorescence were nearly the same among these cells. These oscillations directly reflect enzymatic activities in the glycolytic pathway, thus can be a useful index for evaluating the Warburg effect in cancer cells ( 49 , 50 ). So far, glycolytic oscillations have not been reported in cancer patients or in healthy people, and thus it is challenging to observe their oscillations in vivo and to characterize them across human cancer types.…”

Section: Metabolic Oscillations In Cancer and Other Cellsmentioning

confidence: 99%

“…Glycolytic oscillations in cancer cells were exhibited when glucose, as the only carbon source, was added to glucose-starved cells ( 48 , 50 ). On the other hand, cancers prefer alternative nutrients, such as acetate and fatty acids, in addition to glucose as the source of ATP production ( 52 – 54 ).…”

Section: Metabolic Oscillations In Cancer and Other Cellsmentioning

confidence: 99%

“…Little is known about the glycolytic and mitochondrial interactions in cancer cells when they exhibit glycolytic oscillations ( 48 – 50 ). We assume that extracellular glucose is metabolized to lactate through glycolysis and fermentation without entering the TCA cycle in glucose-starved cancer cells under the experimental conditions of glycolytic oscillations ( 48 ).…”

Section: Metabolic Oscillations In Cancer and Other Cellsmentioning

confidence: 99%

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Oscillations and Dynamic Symbiosis in Cellular Metabolism in Cancer

Amemiya

Yamaguchi²

2022

Front. Oncol.

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The grade of malignancy differs among cancer cell types, yet it remains the burden of genetic studies to understand the reasons behind this observation. Metabolic studies of cancer, based on the Warburg effect or aerobic glycolysis, have also not provided any clarity. Instead, the significance of oxidative phosphorylation (OXPHOS) has been found to play critical roles in aggressive cancer cells. In this perspective, metabolic symbiosis is addressed as one of the ultimate causes of the grade of cancer malignancy. Metabolic symbiosis gives rise to metabolic heterogeneities which enable cancer cells to acquire greater opportunities for proliferation and metastasis in tumor microenvironments. This study introduces a real-time new imaging technique to visualize metabolic symbiosis between cancer-associated fibroblasts (CAFs) and cancer cells based on the metabolic oscillations in these cells. The causality of cellular oscillations in cancer cells and CAFs, connected through lactate transport, is a key point for the development of this novel technique.

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Metabolic Oscillations and Glycolytic Phenotypes of Cancer Cells

Amemiya

Shibata

Yamaguchi³

2023

IJMS

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Cancer cells show several metabolic phenotypes depending on the cancer types and the microenvironments in tumor tissues. The glycolytic phenotype is one of the hallmarks of cancer cells and is considered to be one of the crucial features of malignant cancers. Here, we show glycolytic oscillations in the concentrations of metabolites in the glycolytic pathway in two types of cancer cells, HeLa cervical cancer cells and DU145 prostate cancer cells, and in two types of cellular morphologies, spheroids and monolayers. Autofluorescence from nicotinamide adenine dinucleotide (NADH) in cells was used for monitoring the glycolytic oscillations at the single-cell level. The frequencies of NADH oscillations were different among the cellular types and morphologies, indicating that more glycolytic cancer cells tended to exhibit oscillations with higher frequencies than less glycolytic cells. A mathematical model for glycolytic oscillations in cancer cells reproduced the experimental results quantitatively, confirming that the higher frequencies of oscillations were due to the higher activities of glycolytic enzymes. Thus, glycolytic oscillations are expected as a medical indicator to evaluate the malignancy of cancer cells with glycolytic phenotypes.

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Glycolytic Oscillations in Cancer Cells

Cited by 3 publications

References 65 publications

Glycolytic oscillations in HeLa cervical cancer cell spheroids

Glycolytic oscillations in HeLa cervical cancer cell spheroids

Oscillations and Dynamic Symbiosis in Cellular Metabolism in Cancer

Metabolic Oscillations and Glycolytic Phenotypes of Cancer Cells

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