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Interferon-alpha decreases cancer stem cell properties and modulates exosomes in malignant melanoma

2023-07-18Journal article Open access
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dc.contributor.authorGarcía-Ortega, María Belén
dc.contributor.authorAparicio, Ernesto
dc.contributor.authorGriñán-Lisón, Carmen
dc.contributor.authorJiménez, Gema
dc.contributor.authorLópez-Ruiz, Elena
dc.contributor.authorPalacios, José Luis
dc.contributor.authorRuiz-Alcalá, Gloria
dc.contributor.authorAlba, Cristina
dc.contributor.authorMartínez, Antonio
dc.contributor.authorBoulaiz, Houria
dc.contributor.authorPerán, Macarena
dc.contributor.authorHackenberg, Michael
dc.contributor.authorBragança, José
dc.contributor.authorCalado, Sofia M.
dc.contributor.authorMarchal, Juan A.
dc.contributor.authorGarcía, María Ángel
dc.date.accessioned2023-08-01T15:31:24Z
dc.date.available2023-08-01T15:31:24Z
dc.date.issued2023-07-18
dc.date.updated2023-07-28T12:21:52Z
dc.description.abstractMalignant melanoma (MM) can spread to other organs and is resistant in part due to the presence of cancer stem cell subpopulations (CSCs). While a controversial high dose of interferon-alpha (IFN-α) has been used to treat non-metastatic high-risk melanoma, it comes with undesirable side effects. In this study, we evaluated the effect of low and high doses of IFN-α on CSCs by analyzing ALDH activity, side population and specific surface markers in established and patient-derived primary cell lines. We also assessed the clonogenicity, migration and tumor initiation capacities of IFN-α treated CSCs. Additionally, we investigated genomic modulations related to stemness properties using microRNA sequencing and microarrays. The effect of IFN-α on CSCs-derived exosomes was also analyzed using NanoSight and liquid chromatography (LC-HRMS)-based metabolomic analysis, among others. Our results showed that even low doses of IFN-α reduced CSC formation and stemness properties, and led to a significant decrease in the ability to form tumors in mice xenotransplants. IFN-α also modulated the expression of genes and microRNAs involved in several cancer processes and metabolomics of released exosomes. Our work suggests the utility of low doses of interferon, combined with the analysis of metabolic biomarkers, as a potential clinical approach against the aggressiveness of CSCs in melanoma.pt_PT
dc.description.sponsorshipThis research was funded by the Ministerio de Ciencia, Innovación y Universidades (MICIU, projects noº MAT2015-62644.C2.2.R and RTI2018-101309-B-C2, FEDER Funds), by the Instituto de Salud Carlos III (PIE16-00045), by Consejería de Economía, Conocimiento, Empresas y Universidad de la Junta de Andalucía and European Regional Development Fund (ERDF), ref. SOMM17/6109/UGR (UCE-PP2017-3), by Consejería de Salud y Familias de la Junta de Andalucía (projects noº PEMP0205-2020 FEDER funds), and by the Chair “Doctors Galera-Requena in cancer stem cell research” (CMC-CTS963). J.L.P. (Ref. FPU15/03682) acknowledge the MICIU for providing a PhD fellowship (FPU).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifierdoi: 10.3390/cancers15143666
dc.identifier.citationCancers 15 (14): 3666 (2023)pt_PT
dc.identifier.doi10.3390/cancers15143666pt_PT
dc.identifier.issn2072-6694
dc.identifier.urihttp://hdl.handle.net/10400.1/19911
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectInterferon-αpt_PT
dc.subjectMalignant melanomapt_PT
dc.subjectCancer stem cellspt_PT
dc.subjectExosomespt_PT
dc.subjectMetabolomicspt_PT
dc.subjectBiomarkerspt_PT
dc.titleInterferon-alpha decreases cancer stem cell properties and modulates exosomes in malignant melanomapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue14pt_PT
oaire.citation.startPage3666pt_PT
oaire.citation.titleCancerspt_PT
oaire.citation.volume15pt_PT
person.familyNameBragança
person.givenNameJosé
person.identifier.ciencia-idAC1D-FA9D-F66F
person.identifier.orcid0000-0001-9566-400X
person.identifier.scopus-author-id6602220001
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication27334e02-e955-4939-b9b5-bdee5b5f9328
relation.isAuthorOfPublication.latestForDiscovery27334e02-e955-4939-b9b5-bdee5b5f9328

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