Exosome-mediated Transfer of αvβ3 Integrin from Tumorigenic to Nontumorigenic Cells Promotes a Migratory Phenotype

The alpha v beta 3 integrin is known to be highly upregulated during cancer progression and promotes a migratory and metastatic phenotype in many types of tumors. We hypothesized that the alpha v beta 3 integrin is transferred through exosomes and, upon transfer, has the ability to support functional aberrations in recipient cells. Here, for the first time, it is demonstrated that alpha v beta 3 is present in exosomes released from metastatic PC3 and CWR22Pc prostate cancer cells. Exosomal beta 3 is transferred as a protein from donor to nontumorigenic and tumorigenic cells as beta 3 protein or mRNA levels remain unaffected upon transcription or translation inhibition in recipient cells. Furthermore, it is shown that upon exosome uptake, de novo expression of an alpha v beta 3 increases adhesion and migration of recipient cells on an alpha v beta 3 ligand, vitronectin. To evaluate the relevance of these findings, exosomes were purified from the blood of TRAMP mice carrying tumors where the expression of alpha v beta 3 is found higher than in exosomes from wild-type mice. In addition, it is demonstrated that alpha v beta 3 is coexpressed with synaptophysin, a biomarker for aggressive neuroendocrine prostate cancer. Implications: Overall this study reveals that the alpha v beta 3 integrin is transferred from tumorigenic to nontumorigenic cells via exosomes, and its de novo expression in recipient cells promotes cell migration on its ligand. The increased expression of alpha v beta 3 in exosomes from mice bearing tumors points to its clinical relevance and potential use as a biomarker. (C) 2016 AACR.