Resistance to targeted therapy is one of the important problems in oncology. The main purpose of the work was to study the exosomes involvement in the progression of the resistance of breast cancer cells.
MCF-7 breast cancer cell line was obtained from the ATCC collection. The cells-derived exosomes were isolated by ultracentrifugation and thoroughly characterised. Protein expression was measured by immunoblotting. To measure AP1 activity gene-reporter assay was used.
The rapamycin-resistant MCF-7 cells were developed under long-term treatment of the cells with the increasing doses of rapamycin. The selected cells named as MCF-7/Rap were characterized with the resistance to rapamycin, and at the same time - the partial resistance to antiestrogen tamoxifen. We have shown that the treatment of the parent MCF-7 cells with exosomes from the resistant MCF-7/Rap cells within 14 days lead to the cross resistance of the MCF-7 cells to rapamycin and tamoxifen. The MCF-7/Rap cells and the cells with the exosome-induced resistance were characterized with the increased expression of mTOR-interacting Raptor protein, activation of Akt and transcriptional factor AP-1.
The results obtained demonstrate the important role of Akt/mTOR signaling in the development of exosome-induced cancer cell resistance to growth signal-targeting anti-tumor drugs.
The authors.
RSF (19-15-00245, resistance studies) and RFBR (18-29-09017, exosome characterization).
All authors have declared no conflicts of interest.