P2X7 promotes metastatic spreading and triggers release of miRNA-containing exosomes and microvesicles from melanoma cells
| Autor: | Anna Pegoraro, Elena Adinolfi, Cristian Bassi, Elisa Orioli, Michele Zanoni, Massimo Negrini, Manuela Ferracin, Elena De Marchi, Francesco Di Virgilio, Emi Dika, Anna Tesei, Marina Capece |
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| Přispěvatelé: | Pegoraro A., De Marchi E., Ferracin M., Orioli E., Zanoni M., Bassi C., Tesei A., Capece M., Dika E., Negrini M., Di Virgilio F., Adinolfi E. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Immunology melanoma microRNA P2RX7 purinergic receptor exosomes Exosomes Exosome Article NO Metastasis Cellular and Molecular Neuroscience Mice medicine Animals Humans Neoplasm Metastasis Receptor Melanoma miRNA Cell Proliferation vesicles Tumor microenvironment Ligand-gated ion channels QH573-671 Chemistry Cell growth Microvesicle Cell Biology Transfection medicine.disease Microvesicles ATP miRNAs P2X7 vesicles melanoma miRNA metastasis exosomes microvesicles ATP Cancer research Receptors Purinergic P2X7 Cytology P2X7 microvesicles Ion channel signalling |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 12, Iss 12, Pp 1-12 (2021) |
| ISSN: | 2041-4889 |
| Popis: | Tumor growth and metastatic spreading are heavily affected by the P2X7 receptor as well as microvesicles and exosomes release into the tumor microenvironment. P2X7 receptor stimulation is known to trigger vesicular release from immune and central nervous system cells. However, P2X7 role in microvesicles and exosomes delivery from tumor cells was never analyzed in depth. Here we show that P2X7 is overexpressed in patients affected by metastatic malignant melanoma and that its expression closely correlates with reduced overall survival. Antagonism of melanoma cell-expressed P2X7 receptor inhibited in vitro anchorage-independent growth and migration and in vivo dissemination and lung metastasis formation. P2X7 stimulation triggered the release of miRNA-containing microvesicles and exosomes from melanoma cells, profoundly altering the nature of their miRNA content, as well as their dimensions and quantity. Among the more than 200 miRNAs that we found up-or-down-modulated for each vesicular fraction tested, we identified three miRNAs, miR-495-3p, miR-376c-3p, and miR-6730-3p, that were enriched in both the exosome and microvesicle fraction in a P2X7-dependent fashion. Interestingly, upon transfection, these miRNAs promoted melanoma cell growth or migration, and their vesicular release was minimized by P2X7 antagonism. Our data unveil an exosome/microvesicle and miRNA-dependent mechanism for the pro-metastatic activity of the P2X7 receptor and highlight this receptor as a suitable prognostic biomarker and therapeutic target in malignant melanoma. |
| Databáze: | OpenAIRE |
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