Exosomes have been shown to transmit drug resistance through delivering miRNAs. Researchers at Nanjing Medical University aimed to explore their roles in breast cancer. Three resistant sublines were established by exposing parental MDA-MB-231 cell line to docetaxel, epirubicin and vinorelbine, respectively. Preneoadjuvant chemotherapy biopsies and paired surgically-resected specimens embedded in paraffin from 23 breast cancer patients were collected. MiRNA expression profiles of the cell lines and their exosomes were evaluated using microarray.
Heatmap of 19 miRNAs in 23 paired patient samples
Every two horizontal rows represent a miRNA, and the first row represent its expression in preneoadjuvant chemotherapy biopsies and the second row represent its expression in paired surgically-resected specimens. Each vertical column corresponds to a sample. PR, partial response; SD, stable disease; and PD, progressive disease
The result showed that most miRNAs in exosomes had a lower expression level than that in cells, however, some miRNAs expressed higher in exosomes than in cells, suggesting a number of miRNAs is concentrated in exosomes. Among the dysregulated miRNAs, 22 miRNAs were consistently up-regulated in exosomes and their cells of origin. The researchers further found that 12 of the 22 miRNAs were significantly up-regulated after preneoadjuvant chemotherapy. Further study of the role of these 12 miRNAs in acquisition of drug resistance is needed to clarify their contribution to chemoresistance.