title: Large oncosomes in human prostate cancer tissues and in the circulation of mice with metastatic disease.
abstract: 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 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.
authors.affiliation: Division of Cancer Biology and Therapeutics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. dolores.divizio@childrens.harvard.edu
authors.forename: Dolores
authors.initials: D
authors.lastname: Di Vizio
authors.forename: Matteo
authors.initials: M
authors.lastname: Morello
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Dudley
authors.forename: Peter W
authors.initials: PW
authors.lastname: Schow
authors.forename: Rosalyn M
authors.initials: RM
authors.lastname: Adam
authors.forename: Samantha
authors.initials: S
authors.lastname: Morley
authors.forename: David
authors.initials: D
authors.lastname: Mulholland
authors.forename: Mirja
authors.initials: M
authors.lastname: Rotinen
authors.forename: Martin H
authors.initials: MH
authors.lastname: Hager
authors.forename: Luigi
authors.initials: L
authors.lastname: Insabato
authors.forename: Marsha A
authors.initials: MA
authors.lastname: Moses
authors.forename: Francesca
authors.initials: F
authors.lastname: Demichelis
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Michael
authors.initials: M
authors.lastname: Klagsbrun
authors.forename: Neil A
authors.initials: NA
authors.lastname: Bhowmick
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Crislyn
authors.initials: C
authors.lastname: D'Souza-Schorey
authors.forename: Michael R
authors.initials: MR
authors.lastname: Freeman
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism; D045744:Cell Line, Tumor; D055252:Cell-Derived Microparticles / Q000473:pathology* / Q000648:ultrastructure; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology* / Q000648:ultrastructure
chemical_list: D000089982:ADP-Ribosylation Factor 6; D051242:Caveolin 1; C000715348:ARF6 protein, human; C000715727:Arf6 protein, mouse