Research Papers:

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

Felix Royo, Patricia Zuñiga-Garcia, Verónica Torrano, Ana Loizaga, Pilar Sanchez-Mosquera, Aitziber Ugalde-Olano, Esperanza González, Ana R. Cortazar, Laura Palomo, Sonia Fernández-Ruiz, Isabel Lacasa-Viscasillas, Maria Berdasco, James D. Sutherland, Rosa Barrio, Amaia Zabala-Letona, Natalia Martín-Martín, Amaia Arruabarrena-Aristorena, Lorea Valcarcel-Jimenez, Alfredo Caro-Maldonado, Jorge Gonzalez-Tampan, Guido Cachi-Fuentes, Manel Esteller, Ana M. Aransay, Miguel Unda, Juan M. Falcón-Pérez and Arkaitz Carracedo _

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Oncotarget. 2016; 7:6835-6846. https://doi.org/10.18632/oncotarget.6899

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Felix Royo1,2,*, Patricia Zuñiga-Garcia1,*, Verónica Torrano1,*, Ana Loizaga3,*, Pilar Sanchez-Mosquera1, Aitziber Ugalde-Olano4, Esperanza González1, Ana R. Cortazar1, Laura Palomo1, Sonia Fernández-Ruiz1, Isabel Lacasa-Viscasillas3, Maria Berdasco5, James D. Sutherland1, Rosa Barrio1, Amaia Zabala-Letona1, Natalia Martín-Martín1, Amaia Arruabarrena-Aristorena1, Lorea Valcarcel-Jimenez1, Alfredo Caro-Maldonado1, Jorge Gonzalez-Tampan3, Guido Cachi-Fuentes3, Manel Esteller5, Ana M. Aransay1,2, Miguel Unda3, Juan M. Falcón-Pérez1,2,6,, Arkaitz Carracedo1,6,7,

1CIC bioGUNE, Bizkaia Technology Park, Biscay, Spain

2Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Spain

3Department of Urology, Basurto University Hospital, Bilbao, Spain

4Department of Pathology, Basurto University Hospital, Bilbao, Spain

5Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain

6Ikerbasque, Basque Foundation for Science, Bizkaia, Spain

7Biochemistry and Molecular Biology Department, University of the Basque Country (UPV/EHU), Bizkaia, Spain

*These authors contributed equally to this work

These authors contributed equally to this work

Correspondence to:

Arkaitz Carracedo, e-mail: [email protected]

Juan M. Falcón-Pérez, e-mail: [email protected]

Keywords: extracellular vesicles, exosomes, prostate cancer, urine biomakers

Received: August 18, 2015     Accepted: November 26, 2015     Published: January 12, 2016


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.

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