Adipocyte-derived Lipids Accumulation In Breast Cancer Cells And The Subsequent Utilizatioin Contribute To Tumor Progression

Objective: To study whether the adipocyte-derived lipids could be transferred into breast cancer cells and the underlying mechanism of subsequent lipolysis and trafficking in breast cancer cells.Methods: A Transwell coculture system was conducted and human breast cancer cells were cultured in the absence or presence of differentiated murine 3T3-L1 adipocytes.Migration/invasion and proliferation abilities were compared between breast cancer cells that cultivated alone and cocultivated with mature adipocytes.Triglyceride(TG)content and lipolytic effect in breast cancer cells were measured,as well as expression of lipases and fatty acids(FAs)transporter.Immunohistochemistry assay was performed to detect the differential expression of adipose triglyceride lipase(ATGL),the rate-limiting lipase for lipolysis of triglyceride,and the fatty acid binding protein 5(FABP5)in breast cancer tissue sections.Finally,ATGL and FABP5 were ablated to investigate its impact on lipolysis and aggressiveness in cocultivated breast cancer cells.Results: TG contents in cocultivated breast cancer cells were obviously increased compared to cells cultivated alone.Accordingly,migration and invasion abilities of cancer cells were significantly enhanced after coculture with adipocytes,accompanied by elevated lipolytic effect and expression of ATGL and FABP5.However,the same phenomenon was not observed if adding lipid emulsion into the culture medium to substitute for adipocytes.In line with cellular experiments,ATGL and FABP5 also had a higher level of expression at the invasive front of breast tumor than central part in tissue specimens.Furthermore,a small molecule inhibitor of ATGL could abrogate the lipolysis process and silence of ATGL and FABP5 attenuated the malignancy of cocultivated breast cancer cells.Conclusion: Lipids originated from tumor-surrounding adipocytes could be transferred into breast cancer cells.It was the adipocytes-cancer cells crosstalk rather than lipids alone that induce the up-regulation of lipases and lipolytic effect in cancer cells to utilize the stored TG for tumor progression.Increased expression of the intracellular fatty acids trafficking protein FABP5 also played an important role during this process.