Does fat provide energy for breast tumour cell invasion and metastasis?

Breast cancer is the most commonly diagnosed cancer in New Zealand women. Obese breast cancer patients are more likely to have tumours with advanced clinical stage and high vascular and lymph node involvement. The tumour microenvironment provides vital support for tumours during development and progression of cancer, yet the local effects of stromal adipocytes on breast cancer cells have been largely overlooked. Recent studies by Dirat et al. (2011) and Bochet et al. (2011) have shown that breast cancer cells co-cultured with adipocytes become more resistant to radio- and chemotherapy, and more invasive. However, little is known about the metabolic changes that occur in breast cancer cells when they are cultured with adipocytes. Nieman et al. (2011) determined that lipids were transferred from omental adipocytes to ovarian cancer cells and were consequently used in β-oxidation. It was hypothesised that β-oxidation is increased in breast cancer to exploit the glycerol and fatty acids released by lipolysis from adipocytes in order to support the migration and invasion of breast cancer cells. In this study, breast cancer cell lines MCF7 (ER+; oestrogen receptor positive) and MDA-MB-231 (ER-/PR-/HER2-; oestrogen, progesterone and human epidermal growth factor receptor negative) were co-cultured with adipocytes isolated from breast adipose tissue. Adipose tissue samples were collected via the Cancer Society Tissue Bank from patients at Christchurch Hospital undergoing surgery for therapeutic mastectomy, prophylactic mastectomy and breast reductions. A Seahorse XF24 Analyser was used to measure oxygen consumption and extracellular acidification, as indicators of oxidative phosphorylation and glycolysis, respectively, in breast cancer cells grown alone or in co-culture with human breast adipocytes. MCF7 cells were found to have upregulated glycolysis after co-culture with adipocytes. Western blotting was used to assess differences in the expression of proteins involved in β-oxidation between breast cancer cells grown alone or in co-culture with adipocytes. Levels of carnitine palmitoyltransferase 1 (CPT1A), a protein involved in translocation of fatty acids into the mitochondrial matrix for β-oxidation, showed no change. However, phosphorylated acetyl-CoA carboxylase (ACC), a key metabolic enzyme that when inhibited relieves inhibition of CPT1A to allow fatty acid translocation into mitochondria, showed increased levels in both MCF7 and MDA-MB-231 cells after co-culture with adipocytes. These results support the concept that breast cancer cell metabolism, specifically glycolysis and β-oxidation, is being altered in the presence of adipocytes to utilise fatty acids and glycerol released by adipocytes during lipolysis