Circulating miRNAs in Small Extracellular Vesicles Secreted by a Human Melanoma Xenograft in Mouse Brains

Loredana Guglielmi, Marta Nardella, Carla Musa, Ingrid Cifola, Manuela Porru, Beatrice Cardinali, Ilaria Iannetti, Chiara Di Pietro, Giulia Bolasco, Valentina Palmieri, Laura Vilardo, Nicolò Panini, Fabrizio Bonaventura, Massimiliano Papi, Ferdinando Scavizzi, Marcello Raspa, Carlo Leonetti, Germana Falcone, Armando Felsani, Igea D'Agnano

Research output: Contribution to journalArticlepeer-review

Abstract

The identification of liquid biomarkers remains a major challenge to improve the diagnosis of melanoma patients with brain metastases. Circulating miRNAs packaged into tumor-secreted small extracellular vesicles (sEVs) contribute to tumor progression. To investigate the release of tumor-secreted miRNAs by brain metastasis, we developed a xenograft model where human metastatic melanoma cells were injected intracranially in nude mice. The comprehensive profiles of both free miRNAs and those packaged in sEVs secreted by the melanoma cells in the plasma demonstrated that most (80%) of the sEV-associated miRNAs were also present in serum EVs from a cohort of metastatic melanomas, included in a publicly available dataset. Remarkably, among them, we found three miRNAs (miR-224-5p, miR-130a-3p and miR-21-5p) in sEVs showing a trend of upregulation during melanoma progression. Our model is proven to be valuable for identifying miRNAs in EVs that are unequivocally secreted by melanoma cells in the brain and could be associated to disease progression.

Original languageEnglish
JournalCancers
Volume12
Issue number6
DOIs
Publication statusPublished - Jun 19 2020

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