@article{96b9a2f68cb84c5abf00c0a8b97cd4a8,
title = "Pyruvate secreted from patient-derived cancer-associated fibroblasts supports survival of primary lymphoma cells",
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.",
author = "Akihiko Sakamoto and Shunsuke Kunou and Kazuyuki Shimada and Makoto Tsunoda and Tomohiro Aoki and Chisako Iriyama and Akihiro Tomita and Shigeo Nakamura and Fumihiko Hayakawa and Hitoshi Kiyoi",
note = "Funding Information: H.K. has received research funding from Chugai Pharmaceutical Co., Ltd, Bristol-Myers Squibb, Kyowa Hakko Kirin Co., Ltd, Zenyaku Kogyo Co., Ltd, FUJIFILM Corporation, Nippon Boehringer Ingelheim Co., Ltd, Astellas Pharma Inc. and Celgene Corporation, consulting fees from Astellas Pharma Inc. and Daiichi Sankyo Co., Ltd, and honoraria from Bristol-Myers Squibb, Pfizer Japan Inc. and Astellas Pharma Inc. Funding Information: Saori Kanamori (Nagoya University) for assistance with laboratory work. This work was supported by the Program to Disseminate Tenure Tracking System, MEXT, Japan, by a JSPS Grant-in-Aid for Young Scientists (B) 26860724 and Grant-in-Aid for Scientific Research (C) 17K09922, by the Practical Research for Innovative Cancer Control, MHLW/AMED, Japan, and by The Hori Sciences and Arts Foundation grant to K.S., and by a JSPS Grant-in-Aid for Scientific Research (C) 17K08234 grant to M.T. Funding Information: Ministry of Education, Culture, Sports, Science and Technology; Japan Agency for Medical Research and Development; The Hori Sciences and Arts Foundation; Japan Society for the Promotion of Science; Grant-in-Aid for Scientific Research, Grant/Award Number: 17K08234, 17K09922; Grant-in-Aid for Young Scientists, Grant/Award Number: 26860724 Publisher Copyright: {\textcopyright} 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.",
year = "2019",
month = jan,
doi = "10.1111/cas.13873",
language = "English",
volume = "110",
pages = "269--278",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "1",
}