The αvβ6 Integrin Is Transferred Intercellularly via Exosomes

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