Evidence map›Paper›PMID 41516199›Full record

ArticleInternational journal of molecular sciences2025

Influence of the Cholinergic System on the Pathogenesis of Glioblastoma: Impact of the Neutrophil Granulocytes.

Alejandra Infante Cruz, Paula María Saibene Vélez, Cynthia Arasanz, Micaela Rosato, Federico Remes Lenicov, Juan Iturrizaga, Martín Abelleyro, Marianela Candolfi, Eleonora Regueira, Gladys Hermida and 7 more

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
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

17 authors.

Alejandra Infante CruzInstituto de Medicina Experimental (IMEX-CONICET)-Academia Nacional de Medicina, Buenos Aires C1425AUM, Argentina.ORCID 0000-0001-5865-0346
Paula María Saibene VélezInstituto de Medicina Experimental (IMEX-CONICET)-Academia Nacional de Medicina, Buenos Aires C1425AUM, Argentina.ORCID 0009-0006-3580-9901
Cynthia ArasanzInstituto de Medicina Experimental (IMEX-CONICET)-Academia Nacional de Medicina, Buenos Aires C1425AUM, Argentina.
Micaela RosatoInstituto de Medicina Experimental (IMEX-CONICET)-Academia Nacional de Medicina, Buenos Aires C1425AUM, Argentina.ORCID 0009-0004-4176-3976
Federico Remes LenicovInstituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires C1053ABH, Argentina.ORCID 0000-0003-4108-6341
Juan IturrizagaDivisión Neurocirugía, Instituto de Investigaciones Médicas A Lanari, Universidad de Buenos Aires, Buenos Aires C1053ABH, Argentina.ORCID 0009-0003-3244-8512
Martín AbelleyroInstituto de Medicina Experimental (IMEX-CONICET)-Academia Nacional de Medicina, Buenos Aires C1425AUM, Argentina.ORCID 0000-0002-9961-9414
Marianela CandolfiInstituto de Investigaciones Biomédicas (INBIOMED UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1053ABH, Argentina.ORCID 0000-0002-0843-6568
Eleonora RegueiraLaboratorio de Biología de Anfibios-Histología Animal, Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires C1053ABH, Argentina.ORCID 0000-0002-0572-197X
Gladys HermidaLaboratorio de Biología de Anfibios-Histología Animal, Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires C1053ABH, Argentina.ORCID 0000-0003-0794-9772
Mónica VermeulenInstituto de Medicina Experimental (IMEX-CONICET)-Academia Nacional de Medicina, Buenos Aires C1425AUM, Argentina.ORCID 0000-0002-4984-6555
Silvia BernerServicio de Neurocirugía de la Clínica y Maternidad Santa Isabel, Buenos Aires C1406DKG, Argentina.ORCID 0000-0003-1801-469X
Francisco José BarrantesMolecular Neurobiology Division, BIOMED UCA-CONICET, Buenos Aires C1107AAZ, Argentina.ORCID 0000-0002-4745-681X
Silvia de la VegaSección Anatomía Patológica del Hospital de Quemados "Arturo U. Illia" CABA, Buenos Aires C1424BSD, Argentina.
Carolina JancicInstituto de Medicina Experimental (IMEX-CONICET)-Academia Nacional de Medicina, Buenos Aires C1425AUM, Argentina.ORCID 0000-0001-9222-9571
Marcela Solange VillaverdeUnidad de Transferencia Genética y Laboratorio de Metabolismo, Departamento de Biología, Facultad de Medicina, Instituto de Oncología Ángel H. Roffo, Área Investigación, Universidad de Buenos Aires, Buenos Aires C1053ABH, Argentina.ORCID 0000-0002-0242-9228
Gabriela Verónica SalamoneInstituto de Medicina Experimental (IMEX-CONICET)-Academia Nacional de Medicina, Buenos Aires C1425AUM, Argentina.ORCID 0000-0002-0438-1942

Funding

Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación 03811
6 · The paper itself

Abstract

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Since numerous studies highlight the significance of cholinergic system components in tumor development, acetylcholine (ACh) and the differential activation of its receptors could play a crucial role in GBM progression. The aim of this study was to test this hypothesis by assessing the relevance of the cholinergic system in GBM cells and their microenvironment. We analyzed bulk RNA-seq expression data using the TIMER2.0 web server, focusing on the impact of patient survival in relation to muscarinic receptors (CHRM) and neutrophil infiltration in low-grade glioma (LGG) and GBM. Our analysis revealed a marked decrease in survival associated with all CHRMs, particularly in LGG. Moreover, GBM showed higher neutrophil infiltration and reduced survival, especially in relation to CHRM3. These findings were validated in the U251 cell line and in human GBM tumor biopsies (GBM-b), which also displayed CHRM3 expression. Additionally, we show that GBM cells exposed to cholinergic stimulation exhibited increased vascular endothelial growth factor (VEGF), IL-8 production, and PD-L1 expression, while the VEGF increase was blocked by tiotropium (Tio), a CHRM3 antagonist. Similarly, polymorphonuclear cells from GBM patients (PMN-p) displayed increased PD-L1 expression and IL-8 production upon cholinergic stimulation. Finally, as we previously reported on the relevance of thymic stromal lymphopoietin (TSLP) in GBM pathophysiology, here, we found that TSLP upregulated CHRM3 expression. Our findings highlight the importance of the cholinergic system in the tumor microenvironment, where it may act directly on tumor cells or influence neutrophil physiology, thereby modulating tumor progression.

Indexed as

Brain NeoplasmsGlioblastomaGranulocytesNeutrophilsAcetylcholineAcetylcholinesteraseApoptosisBiopsyCell Line, TumorCholine O-AcetyltransferaseCholinergic AntagonistsGene Expression Regulation, NeoplasticHumansReceptors, MuscarinicTumor MicroenvironmentVascular Endothelial Growth Factor AAcetylcholineAcetylcholinesteraseCholine O-AcetyltransferaseCholinergic AntagonistsReceptors, MuscarinicVascular Endothelial Growth Factor AacetylcholineglioblastomaM3 muscarinic acetylcholine receptorneutrophils

Identifiers

PMID41516199
PMCPMC12785807

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.