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Study of ferroptosis transmission by small extracellular vesicles in epithelial ovarian cancer cells

C Alarcón-Veleiro(1,2,3) R Mato-Basalo(1,2,3) S Lucio-Gallego(1,2,3) M Quindós-Varela(3) T Al-Qatarneh(1,2,3) A Vizoso(1,2,3) M C Arufe(1,2,3) J A Fafián-Labora(1,2,3)


Epithelial ovarian cancer (EOC) is the deadliest gynecologic cancer in women and current treatment involves surgical reduction of tumors followed by combination chemotherapy. Although treatment is effective, many EOCs recur and develop chemoresistance. In the last year, ferroptosis, a novel form of regulated cell death featured by the accumulation of iron and toxic species of lipid metabolism in cells, has emerged as a promising anti-tumor strategy for EOC treatment. This process has a high potential to become a complementary treatment to the current anti-tumour strategies to eliminate resistant cells and to avoid the relapse. Cancer cells, like other cells in the body, release small extracellular vesicles (sEVs) that allow the transport of substances from the cells themselves to communicate with their environment. Here, we shown the transmission of ferroptosis in epithelial ovarian cancer cells (OVCA) through sEV.

We evaluate the colony formation capacity, viability and ferroptotic parameters as MDA levels, GSH/GSSG ratio and intracellular Fe2+ levels on OVCA cells treated with supernantant (SN) and sEVs from F-OVCA cells. We found the sEV from F-OVCA treatment decrease the colony formation capacity, the cell viability and GSH/GSSG ratio and increase the MDA and Fe2+ levels. However, SN fraction doesn’t induce ferroptosis process. Our results demonstrate the capacity of sEV to regulate ferroptosis by paracrine way in OVCA cells. Thus, we discovered the importance of the sEV in the communication between cells in OVCA which would mediate the ferroptosis process.

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