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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)269-278
Number of pages10
JournalCancer Science
Volume110
Issue number1
DOIs
Publication statusPublished - 01-01-2019

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Pyruvic Acid
Lymphoma
Survival
Cell Survival
Citric Acid Cycle
Glycolysis
Neoplasms
Tumor Microenvironment
Metabolome
Coculture Techniques
Cancer-Associated Fibroblasts
Energy Metabolism
Reactive Oxygen Species
Neoplasm Metastasis
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Sakamoto, A., Kunou, S., Shimada, K., Tsunoda, M., Aoki, T., Iriyama, C., ... Kiyoi, H. (2019). Pyruvate secreted from patient-derived cancer-associated fibroblasts supports survival of primary lymphoma cells. Cancer Science, 110(1), 269-278. https://doi.org/10.1111/cas.13873
Sakamoto, Akihiko ; Kunou, Shunsuke ; Shimada, Kazuyuki ; Tsunoda, Makoto ; Aoki, Tomohiro ; Iriyama, Chisako ; Tomita, Akihiro ; Nakamura, Shigeo ; Hayakawa, Fumihiko ; Kiyoi, Hitoshi. / Pyruvate secreted from patient-derived cancer-associated fibroblasts supports survival of primary lymphoma cells. In: Cancer Science. 2019 ; Vol. 110, No. 1. pp. 269-278.
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Sakamoto, A, Kunou, S, Shimada, K, Tsunoda, M, Aoki, T, Iriyama, C, Tomita, A, Nakamura, S, Hayakawa, F & Kiyoi, H 2019, 'Pyruvate secreted from patient-derived cancer-associated fibroblasts supports survival of primary lymphoma cells' Cancer Science, vol. 110, no. 1, pp. 269-278. https://doi.org/10.1111/cas.13873

Pyruvate secreted from patient-derived cancer-associated fibroblasts supports survival of primary lymphoma cells. / Sakamoto, Akihiko; Kunou, Shunsuke; Shimada, Kazuyuki; Tsunoda, Makoto; Aoki, Tomohiro; Iriyama, Chisako; Tomita, Akihiro; Nakamura, Shigeo; Hayakawa, Fumihiko; Kiyoi, Hitoshi.

In: Cancer Science, Vol. 110, No. 1, 01.01.2019, p. 269-278.

Research output: Contribution to journalArticle

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AU - Sakamoto, Akihiko

AU - Kunou, Shunsuke

AU - Shimada, Kazuyuki

AU - Tsunoda, Makoto

AU - Aoki, Tomohiro

AU - Iriyama, Chisako

AU - Tomita, Akihiro

AU - Nakamura, Shigeo

AU - Hayakawa, Fumihiko

AU - Kiyoi, Hitoshi

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