Large Oncosomes in Human Prostate Cancer Tissues and in the Circulation of Mice with Metastatic Disease.
- Di Vizio D
- Morello M
- Dudley AC
- Schow PW
- Adam RM
- Morley S
- Mulholland D
- Rotinen M
- Hager MH
- Moses MA
- Demichelis F
- Lisanti MP
- Wu H
- Klagsbrun M
- Bhowmick NA
- Rubin MA
- D'Souza Schorey C
- Freeman MR
- INSABATO, LUIGI
DOIAbstract
Oncosomes are tumor-derived microvesicles that transmit signaling complexes between cell and tissue compartments. Herein, we show that amoeboid tumor cells export large (1- to 10-μm diameter) vesicles, derived from bulky cellular protrusions, that contain metalloproteinases, RNA, caveolin-1, and the GTPase ADP-ribosylation factor 6, and are biologically active toward tumor cells, endothelial cells, and fibroblasts. We describe methods by which large oncosomes can be selectively sorted by flow cytometry and analyzed independently of vesicles <1 μm. Structures resembling large oncosomes were identified in the circulation of different mouse models of prostate cancer, and their abundance correlated with tumor progression. Similar large vesicles...
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