Exosomes from bulk and stem cells from human prostate cancer have a differential microRNA content that contributes cooperatively over local and pre-metastatic niche

Abstract

// Catherine A. Sánchez 1 , Eliana I. Andahur 1,2 , Rodrigo Valenzuela 3 , Enrique A. Castellón 3 , Juan A. Fullá 1 , Christian G. Ramos 1 and Juan C. Triviño 4 1 Urology Department, Las Condes Clinic, Santiago, Chile 2 Faculty of Science, University of Chile, Santiago, Chile 3 Faculty of Medicine, University of Chile, Santiago, Chile 4 Sistemas Genómicos, Valencia, España Correspondence to: Catherine A. Sánchez, email: // Keywords : prostate cancer, miRNAs, exosomes, next generation sequencing, niche Received : June 17, 2015 Accepted : November 25, 2015 Published : December 09, 2015 Abstract The different prostate cancer (PCa) cell populations (bulk and cancer stem cells, CSCs) release exosomes that contain miRNAs that could modify the local or premetastatic niche. The analysis of the differential expression of miRNAs in exosomes allows evaluating the differential biological effect of both populations on the niche, and the identification of potential biomarkers and therapeutic targets. Five PCa primary cell cultures were established to originate bulk and CSCs cultures. From them, exosomes were purified by precipitation for miRNAs extraction to perform a comparative profile of miRNAs by next generation sequencing in an Illumina platform. 1839 miRNAs were identified in the exosomes. Of these 990 were known miRNAs, from which only 19 were significantly differentially expressed: 6 were overexpressed in CSCs and 13 in bulk cells exosomes. miR-100-5p and miR-21-5p were the most abundant miRNAs. Bioinformatics analysis indicated that differentially expressed miRNAs are highly related with PCa carcinogenesis, fibroblast proliferation, differentiation and migration, and angiogenesis. Besides, miRNAs from bulk cells affects osteoblast differentiation. Later, their effect was evaluated in normal prostate fibroblasts (WPMY-1) where transfection with miR-100-5p, miR-21-5p and miR-139-5p increased the expression of metalloproteinases (MMPs) -2, -9 and -13 and RANKL and fibroblast migration. The higher effect was achieved with miR21 transfection. As conclusion, miRNAs have a differential pattern between PCa bulk and CSCs exosomes that act collaboratively in PCa progression and metastasis. The most abundant miRNAs in PCa exosomes are interesting potential biomarkers and therapeutic targets.