The αvβ3 integrin is known to be highly up-regulated during cancer progression and promotes a migratory and metastatic phenotype in many types of tumors. We hypothesized that the αvβ3 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 αvβ3 is present in exosomes released from metastatic PC3 and CWR22Pc prostate cancer cells. Exosomal αvβ3 is transferred as a protein from donor to non-tumorigenic and tumorigenic cells since the β3 protein or mRNA levels remain unaffected upon transcription and translation inhibition in recipient cells. Furthermore, it is shown that upon exosome uptake, de novo expression of αvβ3 increases adhesion and migration of recipient cells on αvβ3 ligand, vitronectin. To evaluate the relevance of these findings, exosomes were purified from the blood of TRAMP mice carrying tumors where the expression of αvβ3 is found higher than in exosomes from wild-type mice. In addition, it is demonstrated that αvβ3 is co-expressed with synaptophysin, a biomarker for aggressive neuroendocrine prostate cancer.
Implications
Overall this study reveals that the αvβ3 integrin is transferred from tumorigenic to non-tumorigenic and cancer cells via exosomes, and its de novo expression in recipient cells promotes cell migration on its ligand. The increased expression of αvβ3 in exosomes from mice bearing tumors points to its clinical relevance and potential use as a biomarker.