title: The αvβ6 integrin is transferred intercellularly via exosomes.
abstract: Exosomes, cell-derived vesicles of endosomal origin, are continuously released in the extracellular environment and play a key role in intercellular crosstalk. In this study, we have investigated whether transfer of integrins through exosomes between prostate cancer (PrCa) cells occurs and whether transferred integrins promote cell adhesion and migration. Among others, we have focused on the αvβ6 integrin, which is not detectable in normal human prostate but is highly expressed in human primary PrCa as well as murine PrCa in Pten(pc-/-) mice. After confirming the fidelity of the exosome preparations by electron microscopy, density gradient, and immunoblotting, we determined that the αvβ6 integrin is actively packaged into exosomes isolated from PC3 and RWPE PrCa cell lines. We also demonstrate that αvβ6 is efficiently transferred via exosomes from a donor cell to an αvβ6-negative recipient cell and localizes to the cell surface. De novo αvβ6 expression in an αvβ6-negative recipient cell is not a result of a change in mRNA levels but is a consequence of exosome-mediated transfer of this integrin between different PrCa cells. Recipient cells incubated with exosomes containing αvβ6 migrate on an αvβ6 specific substrate, latency-associated peptide-TGFβ, to a greater extent than cells treated with exosomes in which αvβ6 is stably or transiently down-regulated by shRNA or siRNA, respectively. Overall, this study shows that exosomes from PrCa cells may contribute to a horizontal propagation of integrin-associated phenotypes, which would promote cell migration, and consequently, metastasis in a paracrine fashion.
authors.affiliation: From the Prostate Cancer Discovery and Development Program,; Department of Cancer Biology, Sidney Kimmel Cancer Center, and.
authors.forename: Carmine
authors.initials: C
authors.lastname: Fedele
authors.affiliation: From the Prostate Cancer Discovery and Development Program,; Department of Cancer Biology, Sidney Kimmel Cancer Center, and.
authors.forename: Amrita
authors.initials: A
authors.lastname: Singh
authors.affiliation: From the Prostate Cancer Discovery and Development Program,; Department of Cancer Biology, Sidney Kimmel Cancer Center, and.
authors.forename: Brad J
authors.initials: BJ
authors.lastname: Zerlanko
authors.affiliation: Department of Cancer Biology, Sidney Kimmel Cancer Center, and; Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107. Electronic address: Lucia.Languino@jefferson.edu.
authors.forename: Renato V
authors.initials: RV
authors.lastname: Iozzo
authors.affiliation: From the Prostate Cancer Discovery and Development Program,; Department of Cancer Biology, Sidney Kimmel Cancer Center, and.
authors.forename: Lucia R
authors.initials: LR
authors.lastname: Languino
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D055354:Exosomes / Q000737:chemistry*; D015870:Gene Expression; D006801:Humans; D016023:Integrins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019899:Paracrine Communication / Q000235:genetics; D014162:Transfection / Q000379:methods*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D016023:Integrins; D053773:Transforming Growth Factor beta1; C073878:integrin alphavbeta6
keywords: Adhesion; Cell Adhesion; Exosome; Extracellular Matrix; Integrin; Prostate Cancer; Tetraspanin