Evidence map›Paper›PMID 33237352›Full record

ArticleCellular and molecular life sciences : CMLS2021

uPAR-expressing melanoma exosomes promote angiogenesis by VE-Cadherin, EGFR and uPAR overexpression and rise of ERK1,2 signaling in endothelial cells.

Alessio Biagioni, Anna Laurenzana, Beatrice Menicacci, Silvia Peppicelli, Elena Andreucci, Francesca Bianchini, Daniele Guasti, Paolo Paoli, Simona Serratì, Alessandra Mocali and 5 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

49 citing papers in PubMed, 59 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

15 authors at 2 institutions in 1 country.

Alessio Biagioni *Department of Experimental and Clinical Biomedical Sciences, Section of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni, 50, 50134, Florence, Italy.
Anna Laurenzana *Department of Experimental and Clinical Biomedical Sciences, Section of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni, 50, 50134, Florence, Italy.
Beatrice MenicacciDepartment of Experimental and Clinical Biomedical Sciences, Section of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni, 50, 50134, Florence, Italy.
Silvia PeppicelliDepartment of Experimental and Clinical Biomedical Sciences, Section of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni, 50, 50134, Florence, Italy.
Elena AndreucciDepartment of Experimental and Clinical Biomedical Sciences, Section of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni, 50, 50134, Florence, Italy.
Francesca BianchiniDepartment of Experimental and Clinical Biomedical Sciences, Section of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni, 50, 50134, Florence, Italy.
Daniele GuastiDepartment of Experimental and Clinical Medicine, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
Paolo PaoliDepartment of Experimental and Clinical Biomedical Sciences, Section of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni, 50, 50134, Florence, Italy.
Simona SerratìNanotecnology Laboratory, National Cancer Research Centre, IRCCS "Giovanni Paolo II", Viale Orazio Flacco, 65, 70124, Bari, Italy.
Alessandra MocaliDepartment of Experimental and Clinical Biomedical Sciences, Section of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni, 50, 50134, Florence, Italy.
Lido CaloriniDepartment of Experimental and Clinical Biomedical Sciences, Section of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni, 50, 50134, Florence, Italy.
Mario Del RossoDepartment of Experimental and Clinical Biomedical Sciences, Section of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni, 50, 50134, Florence, Italy.
Gabriella FibbiDepartment of Experimental and Clinical Biomedical Sciences, Section of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni, 50, 50134, Florence, Italy.
Anastasia ChillàDepartment of Experimental and Clinical Biomedical Sciences, Section of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni, 50, 50134, Florence, Italy. anastasia.chilla@unifi.it.
Francesca MargheriDepartment of Experimental and Clinical Biomedical Sciences, Section of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni, 50, 50134, Florence, Italy. francesca.margheri@unifi.it.ORCID http://orcid.org/0000-0002-7588-503X
University of Florence · ITIstituto Tumori Bari · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Exosomes (Exos) have been reported to promote pre-metastatic niche formation, proliferation, angiogenesis and metastasis. We have investigated the role of uPAR in melanoma cell lines-derived Exos and their pro-angiogenic effects on human microvascular endothelial cells (HMVECs) and endothelial colony-forming cells (ECFCs). Melanoma Exos were isolated from conditioned media of A375 and M6 cells by differential centrifugation and filtration. Tunable Resistive Pulse Sensing (TRPS) and Nanoparticle tracking analysis were performed to analyze dimension and concentration of Exos. The CRISPR-Cas 9 technology was exploited to obtain a robust uPAR knockout. uPAR is expressed in melanoma Exos that are internalized by HMVECs and ECFCs, enhancing VE-Cadherin, EGFR and uPAR expression in endothelial cells that undergo a complete angiogenic program, including proliferation, migration and tube formation. uPAR loss reduced the pro-angiogenic effects of melanoma Exos in vitro and in vivo by inhibition of VE-Cadherin, EGFR and uPAR expression and of ERK1,2 signaling in endothelial cells. A similar effect was obtained with a peptide that inhibits uPAR-EGFR interaction and with the EGFR inhibitor Gefitinib, which also inhibited melanoma Exos-dependent EGFR phosphorylation. This study suggests that uPAR is required for the pro-angiogenic activity of melanoma Exos. We propose the identification of uPAR-expressing Exos as a potentially useful biomarker for assessing pro-angiogenic propensity and eventually monitoring the response to treatment in metastatic melanoma patients.

Indexed as

Signal TransductionAnimalsAntigens, CDCadherin 5CadherinsCell LineEndothelial CellsErbB ReceptorsExosomesGefitinibGene EditingHumansMelanomaMiceMice, SCIDMitogen-Activated Protein Kinase 1Antigens, CDCadherin 5CadherinsEGFR protein, humanErbB ReceptorsGefitinibMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Receptors, Urokinase Plasminogen ActivatorRNA, Small InterferingAngiogenesisEndothelial cellsExosomesMelanoma cellsuPA/uPAR system

Identifiers

PMID33237352
PMCPMC8004497
OpenAlexW3110626189

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.