P2X7 promotes metastatic spreading and triggers release of miRNA-containing exosomes and microvesicles from melanoma cells

Abstract 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...

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Autores principales:	Anna Pegoraro, Elena De Marchi, Manuela Ferracin, Elisa Orioli, Michele Zanoni, Cristian Bassi, Anna Tesei, Marina Capece, Emi Dika, Massimo Negrini, Francesco Di Virgilio, Elena Adinolfi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/47d92cf271a542258cc92c6596ad9022
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spelling	oai:doaj.org-article:47d92cf271a542258cc92c6596ad90222021-11-21T12:03:23ZP2X7 promotes metastatic spreading and triggers release of miRNA-containing exosomes and microvesicles from melanoma cells10.1038/s41419-021-04378-02041-4889https://doaj.org/article/47d92cf271a542258cc92c6596ad90222021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04378-0https://doaj.org/toc/2041-4889Abstract 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.Anna PegoraroElena De MarchiManuela FerracinElisa OrioliMichele ZanoniCristian BassiAnna TeseiMarina CapeceEmi DikaMassimo NegriniFrancesco Di VirgilioElena AdinolfiNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 12, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Anna Pegoraro Elena De Marchi Manuela Ferracin Elisa Orioli Michele Zanoni Cristian Bassi Anna Tesei Marina Capece Emi Dika Massimo Negrini Francesco Di Virgilio Elena Adinolfi P2X7 promotes metastatic spreading and triggers release of miRNA-containing exosomes and microvesicles from melanoma cells
description	Abstract 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.
format	article
author	Anna Pegoraro Elena De Marchi Manuela Ferracin Elisa Orioli Michele Zanoni Cristian Bassi Anna Tesei Marina Capece Emi Dika Massimo Negrini Francesco Di Virgilio Elena Adinolfi
author_facet	Anna Pegoraro Elena De Marchi Manuela Ferracin Elisa Orioli Michele Zanoni Cristian Bassi Anna Tesei Marina Capece Emi Dika Massimo Negrini Francesco Di Virgilio Elena Adinolfi
author_sort	Anna Pegoraro
title	P2X7 promotes metastatic spreading and triggers release of miRNA-containing exosomes and microvesicles from melanoma cells
title_short	P2X7 promotes metastatic spreading and triggers release of miRNA-containing exosomes and microvesicles from melanoma cells
title_full	P2X7 promotes metastatic spreading and triggers release of miRNA-containing exosomes and microvesicles from melanoma cells
title_fullStr	P2X7 promotes metastatic spreading and triggers release of miRNA-containing exosomes and microvesicles from melanoma cells
title_full_unstemmed	P2X7 promotes metastatic spreading and triggers release of miRNA-containing exosomes and microvesicles from melanoma cells
title_sort	p2x7 promotes metastatic spreading and triggers release of mirna-containing exosomes and microvesicles from melanoma cells
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/47d92cf271a542258cc92c6596ad9022
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P2X7 promotes metastatic spreading and triggers release of miRNA-containing exosomes and microvesicles from melanoma cells

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