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.