| First Author | Singh A | Year | 2016 |
| Journal | Mol Cancer Res | Volume | 14 |
| Issue | 11 | Pages | 1136-1146 |
| PubMed ID | 27439335 | Mgi Jnum | J:236872 |
| Mgi Id | MGI:5810028 | Doi | 10.1158/1541-7786.MCR-16-0058 |
| Citation | Singh A, et al. (2016) Exosome-mediated Transfer of alphavbeta3 Integrin from Tumorigenic to Nontumorigenic Cells Promotes a Migratory Phenotype. Mol Cancer Res 14(11):1136-1146 |
| abstractText | The alphavbeta3 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 alphavbeta3 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 alphavbeta3 is present in exosomes released from metastatic PC3 and CWR22Pc prostate cancer cells. Exosomal beta3 is transferred as a protein from donor to nontumorigenic and tumorigenic cells as beta3 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 alphavbeta3 increases adhesion and migration of recipient cells on an alphavbeta3 ligand, vitronectin. To evaluate the relevance of these findings, exosomes were purified from the blood of TRAMP mice carrying tumors where the expression of alphavbeta3 is found higher than in exosomes from wild-type mice. In addition, it is demonstrated that alphavbeta3 is coexpressed with synaptophysin, a biomarker for aggressive neuroendocrine prostate cancer. IMPLICATIONS: Overall this study reveals that the alphavbeta3 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 alphavbeta3 in exosomes from mice bearing tumors points to its clinical relevance and potential use as a biomarker. Mol Cancer Res; 14(11); 1136-46. (c)2016 AACR. |
