Adriamycin and
docetaxel are two agents commonly used in treatment of
breast cancer, but their efficacy is often limited by the emergence of chemoresistance. Recent studies indicate that exosomes act as vehicles for exchange of genetic cargo between heterogeneous populations of
tumor cells, engendering a transmitted drug resistance for
cancer development and progression. However, the specific contribution of
breast cancer-derived exosomes is poorly understood. Here we reinforced other's report that human
breast cancer cell line MCF-7/S could acquire increased survival potential from its resistant variants MCF-7/Adr and MCF-7/Doc. Additionally, exosomes of the latter, A/exo and D/exo, significantly modulated the cell cycle distribution and drug-induced apoptosis with respect to S/exo. Exosomes pre-treated with
RNase were unable to regulate cell cycle and apoptosis resistance, suggesting an
RNA-dependent manner. Microarray and polymerase chain reaction for the
miRNA expression profiles of A/exo, D/exo, and S/exo demonstrated that they loaded selective
miRNA patterns. Following A/exo and D/exo transfer to recipient MCF-7/S, the same
miRNAs were significantly increased in acquired cells. Target gene prediction and pathway analysis showed the involvement of miR-100, miR-222, and miR-30a in pathways implicated in
cancer pathogenesis, membrane vesiculation and
therapy failure. Furthermore, D/exo co-culture assays and
miRNA mimics transfection experiments indicated that miR-222-rich D/exo could alter target gene expression in MCF-7/S. Our results suggest that drug-resistant
breast cancer cells may spread resistance capacity to sensitive ones by releasing exosomes and that such effects could be partly attributed to the intercellular transfer of specific
miRNAs.