RT Journal Article
SR Electronic
T1 Innate extracellular vesicles from melanoma patients suppress β-catenin in tumor cells by miRNA-34a
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201800205
DO 10.26508/lsa.201800205
VO 2
IS 2
A1 Lee, Jung-Hyun
A1 Dindorf, Jochen
A1 Eberhardt, Martin
A1 Lai, Xin
A1 Ostalecki, Christian
A1 Koliha, Nina
A1 Gross, Stefani
A1 Blume, Katja
A1 Bruns, Heiko
A1 Wild, Stefan
A1 Schuler, Gerold
A1 Vera, Julio
A1 Baur, Andreas S
YR 2019
UL http://www.life-science-alliance.org/content/2/2/e201800205.abstract
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.