Obesity is defined as excessive accumulation of adipose tissue and is associated with many chronic diseases, such as cardiovascular disease and type 2 diabetes. Obesity is associated with reduced survival and increased recurrence of breast cancer. The majority of breast tissue is made up of highly dynamic adipocytes, which may be key players in promoting breast progression within the mammary microenvironment through delivering critical metabolic substrates and mediating paracrine signalling – both of which are altered in obesity.
The aim of this project is to investigate how breast cancer cells mobilise metabolic substrates (focusing on free fatty acids) from surrounding ‘lean’ and ‘obese’ adipocytes and determine the reciprocal effects of ‘lean’ and ‘obese’ adipocyte lipolysis on breast cancer (BrCa) growth.
We observed that free fatty acid release from 3T3-L1 adipocytes was enhanced by co-culturing with either MCF-7 (ER+) or MDA-MB-231 (ER-) breast cancer cells resulting in a significant decrease in stored triacylglycerol content. Furthermore, the rate of transfer of fatty acids from ’obese’ adipocytes to BrCa cells was greater compared to ‘lean’. Finally, we observed enhanced proliferation rate and altered fatty acid metabolism in both MCF-7 and MDA-MB-231 cells when co-cultured with ‘obese’ adipocytes.
These data indicate that adipocyte lipolysis, which can be stimulated by breast cancer cells via secretory paracrine factors, provides fatty acids to breast cancer cells, alters lipid partitioning and increases cellular proliferation. Future studies aim to further characterise this paracrine signalling, especially in obesity, to identify potential therapeutic strategies targeting tumour metabolism.