The ?v?6 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 ?v?6 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 ?v?6 integrin is actively packaged into exosomes isolated from PC3 and RWPE PrCa cell lines. We also demonstrate that ?v?6 is efficiently transferred via exosomes from a donor cell to an ?v?6-negative recipient cell and localizes to the cell surface. De novo ?v?6 expression in an ?v?6-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 ?v?6 migrate on an ?v?6 specific substrate, latency-associated peptide-TGF?, to a greater extent than cells treated with exosomes in which ?v?6 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.

SUBMITTER: Fedele C 

PROVIDER: S-EPMC4335196 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature