PT - JOURNAL ARTICLE AU - Jung-Hyun Lee AU - Jochen Dindorf AU - Martin Eberhardt AU - Xin Lai AU - Christian Ostalecki AU - Nina Koliha AU - Stefani Gross AU - Katja Blume AU - Heiko Bruns AU - Stefan Wild AU - Gerold Schuler AU - Julio Vera AU - Andreas S Baur TI - Innate extracellular vesicles from melanoma patients suppress β-catenin in tumor cells by miRNA-34a AID - 10.26508/lsa.201800205 DP - 2019 Apr 01 TA - Life Science Alliance PG - e201800205 VI - 2 IP - 2 4099 - https://www.life-science-alliance.org/content/2/2/e201800205.short 4100 - https://www.life-science-alliance.org/content/2/2/e201800205.full SO - Life Sci. Alliance2019 Apr 01; 2 AB - Upon tumor development, new extracellular vesicles appear in circulation. Our knowledge of their relative abundance, function, and overall impact on cancer development is still preliminary. Here, we demonstrate that plasma extracellular vesicles (pEVs) of non-tumor origin are persistently increased in untreated and post-excision melanoma patients, exhibiting strong suppressive effects on the proliferation of tumor cells. Plasma vesicle numbers, miRNAs, and protein levels were elevated two- to tenfold and detected many years after tumor resection. The vesicles revealed individual and clinical stage-specific miRNA profiles as well as active ADAM10. However, whereas pEV from patients preventing tumor relapse down-regulated β-catenin and blocked tumor cell proliferation in an miR-34a–dependent manner, pEV from metastatic patients lost this ability and stimulated β-catenin–mediated transcription. Cancer-induced pEV may constitute an innate immune mechanism suppressing tumor cell activity including that of residual cancer cells present after primary surgery.