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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The Belousov–Zhabotinsky (BZ) reaction was investigated to elucidate features of oscillations depending on the applied electrical potential, E. A cation-exchange resin bead loaded with the catalyst of the BZ reaction was placed on a platinum plate as a working electrode and then E was applied. We found that global oscillations (GO) and a reduced state coexisted on the bead at a negative value of E and that the source point of GO changed depending on E. The thickness of the reduced state was determined by a yellow colored region which corresponded to the distribution of Br2. The present studies suggest that the distribution of the inhibitor, Br−, which is produced from Br2, plays an important role in the existence of the reduced state and GO, and the source point of GO. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]