Light‐emitting diode irradiation targets aerobic glycolysis in cancer‐associated fibroblasts to inhibit metabolic coupling with colon cancer cells

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Abstract
Background: The concepts examined in tumor metabolism research have been moving away from cancer cells themselves and the tumor microenvironment has become a focus of investigation. Epigenetic changes affecting glucose metabolism in cancer‐associated fibroblasts (CAFs) in the tumor microenvironment regulate the malignancy of cancer cells. Light‐emitting diode (LED) have several functional effects, including anti‐tumor effects, through a variety of mechanisms. We previously reported that blue LED irradiation had an anti‐tumor effect via Opsin 3 that suppress CAF function in vivo and in vitro. However, the detailed mechanism by which LED affect CAF regulation remained unclear.Methods: CAFs were induced from human intestinal fibroblasts co‐cultured with colon cancer cells. Using lactate assays and reverse transcription‐quantitative PCR, the effects of LED irradiation on glycolysis in CAFs were investigated. The effects of LED irradiation for metabolic coupling were evaluated in vitro.Results: Reverse transcription‐quantitative PCR showed higher expression of CAF marker genes in induced CAFs. Blue LED irradiation of induced CAFs suppressed their ability to promote characteristics of tumor malignancy of colon cancer cell line. LED treatment decreased expression of glycolysis markers, including phosphofructokinase and monocarboxylate transporter 4, indicating inhibition of glycolytic activity in CAFs. Extracellular secretion of lactate from CAFs was decreased by LED irradiation.Conclusions: Blue LED irradiation targeted metabolic coupling between CAFs and colon cancer cells, thereby reducing the promotion of tumor progression by CAFs. Blue LED targeting glucose metabolism in CAFs is a promising anti‐cancer treatment option.

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