Evidence map›Paper›PMID 34789738›Full record

ArticleCell death & disease2021

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

Anna Pegoraro, Elena De Marchi, Manuela Ferracin, Elisa Orioli, Michele Zanoni, Cristian Bassi, Anna Tesei, Marina Capece, Emi Dika, Massimo Negrini and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
6.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 93 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 2 countries.

Anna PegoraroDepartment of Medical Sciences, Section of Experimental Medicine, University of Ferrara, Ferrara, Italy.
Elena De MarchiDepartment of Medical Sciences, Section of Experimental Medicine, University of Ferrara, Ferrara, Italy.
Manuela FerracinDepartment of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.ORCID http://orcid.org/0000-0002-1595-6887
Elisa OrioliDepartment of Medical Sciences, Section of Experimental Medicine, University of Ferrara, Ferrara, Italy.
Michele ZanoniIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
Cristian BassiDepartment of Translational Medicine and for Romagna, and "Laboratorio per le Tecnologie delle Terapie Avanzate" (LTTA), University of Ferrara, Ferrara, Italy.
Anna TeseiIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.ORCID http://orcid.org/0000-0002-8351-5952
Marina CapeceDepartment of Cancer Biology and Genetics, College of Medicine, The Ohio State University and James Comprehensive Cancer Center, Columbus, OH, 43210, USA.ORCID http://orcid.org/0000-0002-7624-8059
Emi DikaDepartment of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.ORCID http://orcid.org/0000-0003-3186-2861
Massimo NegriniDepartment of Translational Medicine and for Romagna, and "Laboratorio per le Tecnologie delle Terapie Avanzate" (LTTA), University of Ferrara, Ferrara, Italy.
Francesco Di VirgilioDepartment of Medical Sciences, Section of Experimental Medicine, University of Ferrara, Ferrara, Italy.ORCID http://orcid.org/0000-0003-3566-1362
Elena AdinolfiDepartment of Medical Sciences, Section of Experimental Medicine, University of Ferrara, Ferrara, Italy. elena.adinolfi@unife.it.ORCID http://orcid.org/0000-0001-8129-9929
University of Ferrara · ITIstituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori · ITAzienda USL di Bologna · ITThe Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · USUniversity of Bologna · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

AnimalsCell ProliferationExosomesHumansMelanomaMiceNeoplasm MetastasisReceptors, Purinergic P2X7P2RX7 protein, humanP2rx7 protein, mouseReceptors, Purinergic P2X7

Identifiers

PMID34789738
PMCPMC8599616
OpenAlexW3214468175

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.