Cancer cells with high-metastatic potential promote a glycolytic shift in activated fibroblasts

by Akiko Kogure, Yutaka Naito, Yusuke Yamamoto, Masakazu Yashiro, Tohru Kiyono, Kazuyoshi Yanagihara, Kosei Hirakawa, Takahiro Ochiya

Cancer-associated fibroblasts (CAFs) are activated fibroblasts and are the major stromal component in various types of malignancies. CAFs often undergo metabolic reprogramming to create an appropriate microenvironment for cancer progression. However, it remains unclear whether the metastatic properties of cancer cells affect aerobic glycolysis in stromal cells. Here, we show that gastric cancer (GC) cells with high metastatic potential strongly promote the metabolic switch from oxidative phosphorylation to aerobic glycolysis in fibroblasts. Transcriptome analysis showed that the expression of glycolysis-related genes, such as LDHA and ENO2, significantly changed in fibroblasts when they were cocultured with cancer cells with high metastatic potential compared to fibroblasts incubated with cancer cells with low metastatic potential. Glucose uptake, lactate production and oxygen consumption in fibroblasts were changed by coculture with GC cells with high metastatic potential. Thus, metabolic reprogramming in CAFs may reflect the metastatic properties of GC cells.