Mammary adipocytes protect triple-negative breast cancer cells from ferroptosis

Ferroptosis, a novel non-apoptotic form of cell death, can induce tumor cell death and treatment resistance. Lipid metabolism is closely related to ferroptosis; however, the effect of mammary adipocytes on breast cancer ferroptosis remains to be elucidated. Here, we established the co-culture system of adipocyte-breast cancer cells and revealed the protection of triple-negative breast cancer from ferroptosis by adipocytes. Then, we performed the lipidomics analysis comparing lipid metabolites of co-cultured and normal-cultured cells. Mechanistically, oleic acid secreted from adipocytes inhibited lipid peroxidation and ferroptosis of triple-negative breast cancer cells in the presence of ACSL3. Taken together, mammary adipocytes can protect breast cancer cells from ferroptosis through oleic acid in the presence of ACSL3. These findings could provide new ideas and targets for tumor treatment.

Automated summary

In this study, a co-culture system of mammary adipocytes and breast cancer cells was established, showing that adipocytes can protect triple-negative breast cancer cells from ferroptosis. Lipidomics analysis revealed that oleic acid secreted from adipocytes inhibits lipid peroxidation and ferroptosis of breast cancer cells through ACSL3.