Effect of therapy-induced secretomes on the transcriptome of ovarian cancer cells

Exogenous signals from drug-stressed cancer cells promote acquisition of a more aggressive phenotype of neighboring tumor cells. Recently, we examined how cancer cell secretome changes in response to chemotherapy. We showed that tumor therapy-induced secretomes significantly increased resistance of cancer cells to subsequent cisplatin treatment but we did not observed the same phenomenon on normal fibroblasts. To elucidate how therapy-induced secretomes affect the transcriptomic profiles of recipient tumor cells, we incubated SKOV3 cells for 3 days with secretomes from control or dying cancer cells. The same conditions were used for normal fibroblasts. Enrichment analysis of differentially expressed genes in SKOV3 cells incubated with therapy-induced secretomes identified prominent up-regulation of genes involved in coordination of mitotic processes, G2/M transition checkpoints and DNA repair. These findings demonstrate that under stress condition cancer but not normal cells can secrete signaling molecules into the exracellular space and contribute to the emergence of tumor chemoresistance during short time period. Overall design: We collected secretomes from donor SKOV3 cells and normal fibroblasts treated or untreated with cisplatin. Recipient SKOV3 cells were incubated for 3 days with secretomes from donor SKOV3 cells before and after therapy. Recipient fibroblasts were incubated for 3 days with secretomes from donor fibroblasts before and after therapy. Total RNA was isolated from recipient SKOV3 cells and fibroblasts. Transcriptome profiles for the obtained samples were generated using HiSeq 2500 System (Illumina).