Innate extracellular vesicles from melanoma patients suppress β-catenin in tumor cells by miRNA-34a

Jung Hyun Lee, Jochen Dindorf, Martin Eberhardt, Xin Lai, Christian Ostalecki, Nina Koliha, Stefani Gross, Katja Blume, Heiko Bruns, Stefan Wild, Gerold Schuler, Julio Vera, Andreas S. Baur

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere201800205
JournalLife Science Alliance
Volume2
Issue number2
DOIs
StatePublished - 2019

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