Dataset Information

Transcriptomic profiling of urine extracellular vesicles reveals alterations of CDH3 in prostate cancer.

ABSTRACT: Extracellular vesicles (EV) are emerging structures with promising properties for intercellular communication. In addition, the characterization of EV in biofluids is an attractive source of non-invasive diagnostic, prognostic and predictive biomarkers. Here we show that urinary EV (uEV) from prostate cancer (PCa) patients exhibit genuine and differential physical and biological properties compared to benign prostate hyperplasia (BPH). Importantly, transcriptomics characterization of uEVs led us to define the decreased abundance of Cadherin 3, type 1 (CDH3) transcript in uEV from PCa patients. Tissue and cell line analysis strongly suggested that the status of CDH3 in uEVs is a distal reflection of changes in the expression of this cadherin in the prostate tumor. CDH3 was negatively regulated at the genomic, transcriptional, and epigenetic level in PCa. Our results reveal that uEVs could represent a non-invasive tool to inform about the molecular alterations in PCa.

SUBMITTER: Royo F

PROVIDER: S-EPMC4872752 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Transcriptomic profiling of urine extracellular vesicles reveals alterations of CDH3 in prostate cancer.

Royo Felix F Zuñiga-Garcia Patricia P Torrano Verónica V Loizaga Ana A Sanchez-Mosquera Pilar P Ugalde-Olano Aitziber A González Esperanza E Cortazar Ana R AR Palomo Laura L Fernández-Ruiz Sonia S Lacasa-Viscasillas Isabel I Berdasco Maria M Sutherland James D JD Barrio Rosa R Zabala-Letona Amaia A Martín-Martín Natalia N Arruabarrena-Aristorena Amaia A Valcarcel-Jimenez Lorea L Caro-Maldonado Alfredo A Gonzalez-Tampan Jorge J Cachi-Fuentes Guido G Esteller Manel M Aransay Ana M AM Unda Miguel M Falcón-Pérez Juan M JM Carracedo Arkaitz A

Oncotarget 20160201 6

Extracellular vesicles (EV) are emerging structures with promising properties for intercellular communication. In addition, the characterization of EV in biofluids is an attractive source of non-invasive diagnostic, prognostic and predictive biomarkers. Here we show that urinary EV (uEV) from prostate cancer (PCa) patients exhibit genuine and differential physical and biological properties compared to benign prostate hyperplasia (BPH). Importantly, transcriptomics characterization of uEVs led us ...[more]

PMID: 26771841

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Project description:Simple Summary Prostate cancer is the second most commonly diagnosed cancer and the fifth leading cause of cancer-related death in men. It is a generally slow-growing cancer that—when detected in its early stages—has high chances of successful treatment. Just like all cells, cancerously degenerated cells release extracellular vesicles (EVs) to communicate with other cells. The aim of our research was to specifically isolate prostate cancer-derived EVs from urine, characterize the EV surface markers of a prostate cancer cohort, and assess the potential value of the prostate-specific membrane antigen (PSMA) as a biomarker for liquid biopsy in early cancer diagnostics. Our findings demonstrate that the automated isolation of EVs allows for an overall improvement of the precision in sample purification in comparison to manual isolation, thus optimizing the further characterization of EV surface markers as well as evaluating their use in clinical application. Abstract All cells release extracellular vesicles (EVs) to communicate with adjacent and distant cells. Consequently, circulating EVs are found in all bodily fluids, providing information applicable for liquid biopsy in early cancer diagnosis. Studies observed an overexpression of the membrane-bound prostate-specific membrane antigen (PSMA) on prostate cancer cells. To investigate whether EVs derived from communicating prostate cells allow for reliable conclusions on prostate cancer development, we isolated PSMA-positive, as well as CD9-positive, EVs from cell-free urine with the use of magnetic beads. These populations of EVs were subsequently compared to CD9-positive EVs isolated from female urine in Western blotting, indicating the successful isolation of prostate-derived and ubiquitous EVs, respectively. Furthermore, we developed a device with an adapted protocol that enables an automated immunomagnetic enrichment of EVs of large sample volumes (up to 10 mL), while simultaneously reducing the overall bead loss and hands-on time. With an in-house spotted antibody microarray, we characterized PSMA as well as other EV surface markers of a prostate cohort of 44 urine samples in a more simplified way. In conclusion, the automated and specific enrichment of EVs from urine has a high potential for future diagnostic applications.

Dataset Information

Transcriptomic profiling of urine extracellular vesicles reveals alterations of CDH3 in prostate cancer.

Publications

Transcriptomic profiling of urine extracellular vesicles reveals alterations of CDH3 in prostate cancer.

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