Cimetta, Elisa (2022) EVs from hypoxic NB cells stimulate migration and invasion of target cells via miR-210-3p. [Data Collection]
Collection description
Tumor 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. Here we show that EVs from hypoxic NB cells promote pro-metastasis features in vitro and in an in vivo model. EVs from NB cells cultured at different oxygen tensions did not differ for type and abundance of surface markers and for biophysical properties. However, EVs derived from hypoxic NB cells were more potent than their normoxic counterpart in inducing NB cells migration and colony formation. We characterized and compared the microRNA (miRNA) cargo of EVs from NB cells cultured at different oxygen tensions and found that miR-210-3p was the most upregulated. Mechanistically, we identified that the pro-metastatic features of EVs from hypoxic NB cells derived from a miR-210-3p enrichment in their cargo. Indeed, 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 in vivo zebrafish model. Our data identify a role for hypoxic EVs in the cellular and microenvironmental changes favoring NB dissemination.
10.25430/researchdata.cab.unipd.it.00000701
orcid.org/0000-0002-8632-3999
