期刊
CANCER SCIENCE
卷 110, 期 1, 页码 269-278出版社
WILEY
DOI: 10.1111/cas.13873
关键词
cancer-associated fibroblast; Krebs cycle; lymphoma; pyruvate; reverse Warburg effect
类别
资金
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Agency for Medical Research and Development
- Hori Sciences and Arts Foundation
- Japan Society for the Promotion of Science
- [17K08234]
- [17K09922]
- [26860724]
Cancer-associated fibroblasts (CAF) are a key component in the tumor microenvironment and play functional roles in tumor metastasis and resistance to chemotherapies. We have previously reported that CAF isolated from lymphoma samples increase anaerobic glycolysis and decrease intracellular production of reactive oxygen species, promoting the survival of tumor cells. Herein, we analyzed the mechanisms underlying this support of tumor-cell survival by CAF. As direct contact between lymphoma cells and CAF was not indispensable to survival support, we identified that the humoral factor pyruvate was significantly secreted by CAF. Moreover, survival of lymphoma cells was promoted by the presence of pyruvate, and this promotion was canceled by inhibition of monocarboxylate transporters. Metabolome analysis of lymphoma cells in coculture with CAF demonstrated that intermediates in the citric acid cycle were significantly increased, indicating that tumor cells produced energy by aerobic metabolism. These findings indicate that energy production in lymphoma cells is regulated in coordination not only with anaerobic glycolysis, but also with aerobic metabolism termed the reverse-Warburg effect, involving the secretion of pyruvate from CAF resulting in increased use of the citric acid cycle in lymphoma cells.
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