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 language | English |
|---|---|
| Pages (from-to) | 269-278 |
| Number of pages | 10 |
| Journal | Cancer Science |
| Volume | 110 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 01-01-2019 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Cite this
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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 journal › Article
TY - JOUR
T1 - Pyruvate secreted from patient-derived cancer-associated fibroblasts supports survival of primary lymphoma cells
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
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85057945602&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85057945602&partnerID=8YFLogxK
U2 - 10.1111/cas.13873
DO - 10.1111/cas.13873
M3 - Article
VL - 110
SP - 269
EP - 278
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 1
ER -