Isolation, identification, and characterization of novel nanovesicles.

Extracellular microvesicles (EVs) have been recognized for many potential clinical applications including biomarkers for disease diagnosis. In this study, we identified a major population of EVs by simply screening fluid samples with a nanosizer. Unlike other EVs, this extracellular nanovesicle (named HG-NV, HG-NV stands for HomoGenous nanovesicle as well as for Huang-Ge- nanovesicle) can be detected with a nanosizer with minimal in vitro manipulation and are much more homogenous in size (8-12 nm) than other EVs. A simple filtration platform is capable of separating HG-NVs from peripheral blood or cell culture supernatants. In comparison with corresponding exosome profiles, HG-NVs released from both mouse and human breast tumor cells are enriched with RNAs. Tumor derived HG-NVs are more potent in promoting tumor progression than exosomes. In summary, we identified a major subset of EVs as a previously unrecognized nanovesicle. Tumor cell derived HG-NVs promote tumor progression. Molecules predominantly present in breast tumor HG-NVs have been identified and characterized. This discovery may have implications in advancing both microvesicle biology research and clinical management including potential used as a biomarker.