Journal
CELL CYCLE
Volume 12, Issue 22, Pages 3526-3536Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.26539
Keywords
amoeboid blebbing; microvesicle; filtration; large oncosome; exosome; extracellular vesicles; miRNA; prostate cancer
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Funding
- National Cancer Institute [CA131472 [R00], R01CA143777]
- Steven Spielberg Discovery Fund in Prostate Cancer Research
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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 on cosomes applicable to human plateletpoor plasma, where the presence of caveolin-l-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.
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