Pyruvate secreted from patient-derived cancer-associated fibroblasts supports survival of primary lymphoma cells

Akihiko Sakamoto, Shunsuke Kunou, Kazuyuki Shimada, Makoto Tsunoda, Tomohiro Aoki, Chisako Iriyama, Akihiro Tomita, Shigeo Nakamura, Fumihiko Hayakawa, Hitoshi Kiyoi

研究成果: Article査読

22 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)269-278
ページ数10
ジャーナルCancer science
110
1
DOI
出版ステータスPublished - 01-2019

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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