MCF-7 Drug Resistant Cell Lines Switch Their Lipid Metabolism to Triple Negative Breast Cancer Signature

SIMPLE SUMMARY: Previously, we have demonstrated that lipid and lipoprotein profiles in breast cancer patients are altered compared to a control showing a new link between triglycerides enriched particles and breast cancer, hence suggesting an active role of lipids and their metabolism in this pathology. In this study, we have demonstrated the importance of tumor microenvironment crosstalk as well as the crucial role of lipid transfer between adipose tissue and cancerous cells. Moreover, we have demonstrated that each breast cancer subtype has their specific lipid signature. Interestingly, drug resistant luminal A cell lines switch this metabolic profile to the triple negative lipid signature. Knowledge of these signatures might help us to understand how these specific lipids are related with drug resistance and how it may clarify new treatments in these cancer patients. ABSTRACT: Obesity and adipose tissue have been closely related to a poor cancer prognosis, especially in prostate and breast cancer patients. The ability of transferring lipids from the adipose tissue to the tumor cells is actively linked to tumor progression. However, different types of breast tumor seem to use these lipids in different ways and metabolize them in different pathways. In this study we have tracked by mass spectrometry how palmitic acid from the adipocytes is released to media being later incorporated in different breast cancer cell lines (MDA-MB-231, SKBR3, BT474, MCF-7 and its resistant MCF-7 EPI(R) and MCF-7 TAX(R)). We have observed that different lines metabolize the palmitic acid in a different way and use their carbons in the synthesis of different new lipid families. Furthermore, we have observed that the lipid synthesis pattern varied according to the cell line. Surprisingly, the metabolic pattern of the resistant cells was more related to the TNBC cell line compared to their sensitive cell line MCF-7. These results allow us to determine a specific lipid pattern in different cell lines that later might be used in breast cancer diagnosis and to find a better treatment according to the cancer molecular type.