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Exercise‐induced changes in tumour LDH‐B and MCT1 expression are modulated by oestrogen‐related receptor alpha in breast cancer‐bearing BALB/c mice
Author(s) -
Aveseh Malihe,
Nikooie Rohollah,
Aminaie Mohsen
Publication year - 2015
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp270463
Subject(s) - basigin , lactate dehydrogenase , lactate dehydrogenase a , endurance training , endocrinology , medicine , glycolysis , cancer cell , anaerobic glycolysis , receptor , cancer , alpha (finance) , monocarboxylate transporter , biology , metabolism , chemistry , biochemistry , transporter , enzyme , gene , construct validity , nursing , matrix metalloproteinase , patient satisfaction
Key points Monocarboxylate transporters (MCTs) and lactate dehydrogenase A (LDH‐A) play important roles in sustaining the glycolytic phenotype seen in cancer. Endurance training improves aerobic capacity; however, whether endurance training alters the metabolic phenotype of a solid tumour, from the perspective of lactate metabolism, is yet to be proven. This study showed that endurance training decreases expression of the MCT1 basigin (CD147) and LDH‐A , and also increases LDH‐B expression in solid tumours and attenuates tumour lactate metabolism. Similar results for MCT1 and LDH‐B were found with inhibition of the oestrogen‐related receptor alpha (ERRα). The training effects were not additive to the ERRα effects on MCT1 and LDH‐B expression in the tumour, which indicated that exercise‐induced alterations in MCT1 and LDH‐B expression were modulated by ERRα. These results suggest that endurance training could be a useful tool in cancer therapy, especially in basal‐like and luminal‐like breast carcinomas.Abstract Several factors, including overexpression of lactate dehydrogenase (LDH) and monocarboxylate transporters (MCTs), promote an aerobic lactate production that allows some cancer cells to sustain higher proliferation rates in hostile environments outside the cell. To elucidate the effect of endurance training on the metabolic phenotype of solid tumours, we focused on the tumour expression of LDH‐A, LDH‐B, MCT1, MCT4, oestrogen‐related receptor alpha (ERRα) and LDH isozymes in control (C), trained (T), control+XCT790 (CX) and trained+XCT790 (TX) mice. First, we found that the metabolically altered tumours from the trained animals exhibited lower values for lactate concentration than the control group. The decreased lactate concentration was associated with a shift in the tumour LDH isozyme profile towards LDH‐1. These exercise‐induced changes were also associated with decreases in the expression of the tumour MCT1, ERRα and CD147 in the trained animals. Secondly, the inhibition of ERRα by treatment of MC4‐L2 human breast cancer cells with XCT790 (inverse agonist ligand of ERRα) before injection into the animals not only increased LDH‐B expression in the tumour, but also decreased MCT1 expression in the CX group in comparison to the C group. The effects of ERRα inhibition were not additive to the training effects on the expressions of MCT1 and LDH‐B in the solid tumours. In conclusion, our results suggest that exercise‐induced suppression of ERRα expression modulates alterations in solid tumour expression of LDH‐B and MCT1 and contributes towards the prevention of tumour development.