Mitochondrial metabolism in breast cancer and cancer-associated adipose tissue

Abstract

The metabolic profile of cancer is fraught with controversy, together with the mitochondrial metabolism in the context of cancer progression. Consequently, we examined the mitochondrial metabolism in tumor tissue and cancer-associated adipose tissue (CAAT) from normal-weight and obese premenopausal women with malignant (invasive ductal carcinoma) and benign (fibroadenoma) breast tumors. Mitochondrial copy number (MCN) is decreased in malignant tumor tissue compared to benign controls in both normal-weight and obese women, while in women with benign tumors, MCN is also decreased in obese women. In CAAT, MCN is reduced only in obese women with malignant tumors compared to normal-weight women, with the same trend of MCN decrease in women with benign tumors. Consistent with these findings, the same changes are found in PGC-1α at the level of protein expression. Further, the protein expression of complexes II, III, IV, and ATP synthase is mostly increased in malignant tumor tissue and CAAT, independently of obesity, while the protein expression of complex I in all groups remains unchanged. The protein expression of pyruvate dehydrogenase and citrate synthase is notably reduced in malignant tumor tissue regardless of obesity, but in CAAT, the opposite changes are detected. Moreover, peroxisomal β-oxidation of fatty acids is increased in malignant tumor tissue and CAAT, independently of obesity. In contrast, mitochondrial β-oxidation is increased only in malignant tumor tissue of obese women. Hence, these results indicate a sophisticated organization of metabolism in mitochondria, and cooperation between tumor tissue and CAAT, with the particular influence of obesity on breast cancer progression.