Large oncosomes mediate intercellular transfer of functional microRNA

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 isola...

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Bibliographic Details
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
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Summary: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.
ISSN:1538-4101
1551-4005
DOI:10.4161/cc.26539