The American journal of pathology

1525-2191 181 5 2012 Nov The American journal of pathology Am. J. Pathol. Large oncosomes in human prostate cancer tissues and in the circulation of mice with metastatic disease. 1573-84 10.1016/j.ajpath.2012.07.030 S0002-9440(12)00600-1 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-Îŧm 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 Îŧm. 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 were also identified in human tumor tissues, but they were not detected in the benign compartment. They were more abundant in metastases. Our results suggest that tumor microvesicles substantially larger than exosome-sized particles can be visualized and quantified in tissues and in the circulation, and isolated and characterized using clinically adaptable methods. These findings also suggest a mechanism by which migrating tumor cells condition the tumor microenvironment and distant sites, thereby potentiating advanced disease. Copyright ÂŠ 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. Di Vizio Dolores D Division of Cancer Biology and Therapeutics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. dolores.divizio@childrens.harvard.edu Morello Matteo M Dudley Andrew C AC Schow Peter W PW Adam Rosalyn M RM Morley Samantha S Mulholland David D Rotinen Mirja M Hager Martin H MH Insabato Luigi L Moses Marsha A MA Demichelis Francesca F Lisanti Michael P MP Wu Hong H Klagsbrun Michael M Bhowmick Neil A NA Rubin Mark A MA D'Souza-Schorey Crislyn C Freeman Michael R MR eng K99CA131472 CA NCI NIH HHS United States R00 CA140708 CA NCI NIH HHS United States R01 CA108646 CA NCI NIH HHS United States R01 CA115316 CA NCI NIH HHS United States R01CA143777 CA NCI NIH HHS United States R01DK57691 DK NIDDK NIH HHS United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2012 09 27