dc.contributor
Institut Català de la Salut
dc.contributor
[Lee SY, Egia-Mendikute L, Antoñana-Vildosola A, Velasco-Beltrán P, Bosch A] Cancer Glycoimmunology Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain. [Prieto-Fernández E] Tumor Immunology and Immunotherapy Lab, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Lee, So Young
dc.contributor.author
Prieto-Fernández, Endika
dc.contributor.author
Antoñana Vildosola, Asier
dc.contributor.author
Velasco-Beltrán, Paloma
dc.contributor.author
Bosch Martinez, Alexandre
dc.contributor.author
Egia-Mendikute, Leire
dc.date.accessioned
2025-10-25T05:37:08Z
dc.date.available
2025-10-25T05:37:08Z
dc.date.issued
2025-07-02T07:07:49Z
dc.date.issued
2025-07-02T07:07:49Z
dc.date.issued
2025-04-07
dc.identifier
Lee SY, Prieto-Fernández E, Egia-Mendikute L, Antoñana-Vildosola A, Velasco-Beltrán P, Bosch A, et al. Syndecan-3 positively regulates the pro-inflammatory function of macrophages. Cell Mol Life Sci. 2025 Apr 7;82:145.
dc.identifier
http://hdl.handle.net/11351/13330
dc.identifier
10.1007/s00018-025-05649-1
dc.identifier
001465522000008
dc.identifier.uri
http://hdl.handle.net/11351/13330
dc.description.abstract
Angiogenesis; Cancer; Syndecans
dc.description.abstract
Angiogénesis; Cáncer; Sindecanos
dc.description.abstract
Angiogènesi; Càncer; Sindecans
dc.description.abstract
The tumour microenvironment (TME) is a highly structured ecosystem that surrounds a tumour and plays a crucial role in tumorigenesis. As one of the most abundant cell types in the TME, tumour-associated-macrophages (TAMs) can promote disease progression and resistance to therapy. Syndecan-3 (SDC3) is a cell-surface heparan sulphate proteoglycan expressed by TAMs, although its functional relevance in these cells remains unknown. Here, we demonstrated that pro-inflammatory cytokines drive the expression of SDC3 on the cell surface of macrophages. Genetic ablation of SDC3 in macrophages led to aberrant proliferation, adhesion and expression of CD40 and CD86 surface markers. Moreover, SDC3 defective macrophages exhibited distinctive gene expression patterns, leading to impaired tumour cell phagocytosis and increased tumour cell proliferation. Mechanistically, a decrease in the secretion of pro-inflammatory cytokines was observed in SDC3 KO macrophages, concomitant with impaired T cell effector functions. Additionally, a higher angiogenic capacity was observed in endothelial cells when co-cultured with macrophages deficient for SDC3, possibly mediated through an increased release of VEGFA, PECAM-1 and IL-8 by SDC3 KO cells. Collectively, we have identified SDC3 as a modulator of macrophage functions aiming at supporting a pro-inflammatory and anti-tumour phenotype in these cells.
dc.description.abstract
This research was supported by the European Research Council (ERC) (ERC-2018-StG 804236-NEXTGEN-IO to AP), AECC (LABAE211744PALA to AP), La Caixa Foundation (LCF/PR/HR21/52410009 to AP) and the FERO Foundation. Personal fellowships: Lorena Pérez-Gutiérrez (Juan de la Cierva: JDC2022-048612-I, AECC Talent: TALEN245896PERE), Endika Prieto-Fernández (Ramón y Cajal: RYC2021-031213-I), Asier Antoñana-Vildosola (La Caixa Inphinit: LCF/BQ/DR20/11790022), Paloma Velasco-Beltrán (PRE2020-092342 funded by MCIN/AEI /10.13039/501100011033 and by FSE:”), Alexandre Bosch (AECC: PRDVZ19003BOSC), Borja Jimenez-Lasheras (Basque Government: PRE_2019_1_0320), Ander de Blas (AECC: PRDVZ21640DEBL), Jone Etxaniz-Díaz de Durana (PRE2022-104817 funded by MCIN/AEI /10.13039/501100011033 and by FSE+), Eunate Valdaliso-Díez (PREP2022-000848 funded by MICIU/AEI/10.13039/501100011033 and by ESF+), Alena Gros (Instituto de Salud Carlos III: MS15/00058) and Asís Palazón (RYC2018-024183-I funded by MCIN/AEI /10.13039/501100011033 and by FSE; and PID2022-139344OB-I00 funded by MCIN/ AEI /10.13039/501100011033/ and by FEDER.
dc.format
application/pdf
dc.relation
Cellular and Molecular Life Sciences;82
dc.relation
https://doi.org/10.1007/s00018-025-05649-1
dc.relation
info:eu-repo/grantAgreement/ES/PEICTI2021-2023/RYC2021-031213-I
dc.rights
Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Glicoproteïnes
dc.subject
Cèl·lules - Proliferació
dc.subject
CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Syndecans::Syndecan-3
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PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironment
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DISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation
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ANATOMY::Cells::Cells::Myeloid Cells::Cells::Macrophages
dc.subject
PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Cell Growth Processes::Cell Proliferation
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::glicoproteínas::glicoproteínas de membranas::sindecanos::sindecano-3
dc.subject
FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::microambiente celular::microambiente tumoral
dc.subject
ENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::inflamación
dc.subject
ANATOMÍA::células::células::células mieloides::células::macrófagos
dc.subject
FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::procesos de crecimiento celular::proliferación celular
dc.title
Syndecan-3 positively regulates the pro-inflammatory function of macrophages
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
