miR-210-3p enriched extracellular vesicles from hypoxic neuroblastoma cells stimulate migration and invasion of target cells

Cell & Bioscience

Research

Lorenzo Bova¹  Luca Zanella²  Sara Micheli²  Elisa Cimetta²  Pina Fusco²  Maria Rosaria Esposito²  Giulia Borile³  Giuseppe Germano³  Angelica Bastianello³  Anna Fietta³ 

[1] Department of Industrial Engineering (DII), University of Padua, Via Marzolo 9, 35131, Padua, Italy;Department of Industrial Engineering (DII), University of Padua, Via Marzolo 9, 35131, Padua, Italy;Fondazione Istituto Di Ricerca Pediatrica Città Della Speranza (IRP), Corso Stati Uniti 4, 35127, Padua, Italy;Fondazione Istituto Di Ricerca Pediatrica Città Della Speranza (IRP), Corso Stati Uniti 4, 35127, Padua, Italy;

关键词: Neuroblastoma;    Extracellular vesicles;    miRNA;    Hypoxia;    Metastasis;   

DOI  :  10.1186/s13578-023-01045-z

 received in 2023-02-02, accepted in 2023-05-03,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundTumor hypoxia stimulates release of extracellular vesicles (EVs) that facilitate short- and long-range intercellular communication and metastatization. Albeit hypoxia and EVs release are known features of Neuroblastoma (NB), a metastasis-prone childhood malignancy of the sympathetic nervous system, whether hypoxic EVs can facilitate NB dissemination is unclear.MethodsHere we isolated and characterized EVs from normoxic and hypoxic NB cell culture supernatants and performed microRNA (miRNA) cargo analysis to identify key mediators of EVs biological effects. We then validated if EVs promote pro-metastatic features both in vitro and in an in vivo zebrafish model.ResultsEVs from NB cells cultured at different oxygen tensions did not differ for type and abundance of surface markers nor for biophysical properties. However, EVs derived from hypoxic NB cells (hEVs) were more potent than their normoxic counterpart in inducing NB cells migration and colony formation. miR-210-3p was the most abundant miRNA in the cargo of hEVs; mechanistically, overexpression of miR-210-3p in normoxic EVs conferred them pro-metastatic features, whereas miR-210-3p silencing suppressed the metastatic ability of hypoxic EVs both in vitro and in vivo.ConclusionOur data identify a role for hypoxic EVs and their miR-210-3p cargo enrichment in the cellular and microenvironmental changes favoring NB dissemination.

【 授权许可】

CC BY   
© The Author(s) 2023

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