Large oncosomes mediate intercellular transfer of functional microRNA

• Published in: Cell cycle (Georgetown, Tex.) Tex.), 2013-11, Vol.12 (22), p.3526-3536
• Main Authors: Morello, Matteo, Minciacchi, Valentina, de Candia, Paola, Yang, Julie, Posadas, Edwin, Kim, Hyung, Griffiths, Duncan, Bhowmick, Neil, Chung, Leland, Gandellini, Paolo, Freeman, Michael, Demichelis, Francesca, DiVizio, Dolores
• Format: Article
• Language: English
• Subjects: amoeboid blebbing; Caveolin 1 - metabolism; Cell Line, Tumor; Cell Movement; Cell-Derived Microparticles - metabolism; exosome; extracellular vesicles; Fibroblasts - pathology; Fibroblasts - physiology; filtration; Gene Regulatory Networks; Humans; In Vitro Techniques; large oncosome; Male; MicroRNAs - metabolism; microvesicle; miRNA; prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; RNA Transport; Tumor Microenvironment
• ISSN: 1538-4101; 1551-4005
• DOI: 10.4161/cc.26539

Prostate cancer cells release atypically large extracellular vesicles (EVs), termed large oncosomes, which may play a role in the tumor microenvironment by transporting bioactive molecules across tissue spaces and through the blood stream. In this study, we applied a novel method for selective isolation of large oncosomes applicable to human platelet-poor plasma, where the presence of caveolin-1-positive large oncosomes identified patients with metastatic disease. This procedure was also used to validate results of a miRNA array performed on heterogeneous populations of EVs isolated from tumorigenic RWPE-2 prostate cells and from isogenic non-tumorigenic RWPE-1 cells. The results showed that distinct classes of miRNAs are expressed at higher levels in EVs derived from the tumorigenic cells in comparison to their non-tumorigenic counterpart. Large oncosomes enhanced migration of cancer-associated fibroblasts (CAFs), an effect that was increased by miR-1227, a miRNA abundant in large oncosomes produced by RWPE-2 cells. Our findings suggest that large oncosomes in the circulation report metastatic disease in patients with prostate cancer, and that this class of EV harbors functional molecules that may play a role in conditioning the tumor microenvironment.