Efeito de vesículas extracelulares e cell free DNA de pacientes com câncer de próstata em células normais prostáticas.

Abstract

Prostate cancer (PCa) is one of the major causes of death among men worldwide, and little is known about the disease development and the metastasis process. New clinical approaches have been proposed, aiming to improve the quality of life of prostate cancer patients. Amongst various approaches, liquid biopsies have been distinguished from other techniques, by being less invasive than tissue biopsies. In this technique, tumor cells, extracellular vesicles and circulating DNA fragments can be identified in various biological fluids and used for screening. In addition to their use in the prostate cancer diagnosis, circulating tumor cells, vesicles and DNA, can play a role in pro-tumor events, as the malignant transformation of adjacent cells or in the metastasis process. Based on that information, this work aimed to evaluate the effect of prostate tumor derived extracellular vesicles and circulating DNA in normal prostate cell lines upon 24 h treatment. To this end, we first characterized those molecules, then functional assays were performed, such as cell migration and proliferation, gene expression and metabolomics. Metabolomic analysis was also performed in hope to identify potential biomarkers secreted by normal cells in response to the treatment with circulating tumor DNA. Results demonstrate that extracellular vesicles derived of PCa patients can alter the expression profile of PCa related genes and epithelial mesenchymal transition genes. Increase in cell proliferation and migration was also observed after treatment. Circulating DNA isolated from PCa patients were also capable to alter the gene expression of normal cells, altering as well their metabolic profile. In addition, concentration of cfDNA could separate health individuals and PCa patients with a sensibility of 72% and specificity of 71%. Those data confirm the role of EV and cfDNA derived from PCa patients in malignant cellular events, crucial to the development and progression of the PCa. Furthermore, we demonstrated the potential of EV and cfDNA as diagnostic and therapeutic targets.