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

Detalhes bibliográficos
Autor(a) principal: García-Ortega, María Belén
Data de Publicação: 2023
Outros Autores: Aparicio, Ernesto, Griñán-Lisón, Carmen, Jiménez, Gema, López-Ruiz, Elena, Palacios, José Luis, Ruiz-Alcalá, Gloria, Alba, Cristina, Martínez, Antonio, Boulaiz, Houria, Perán, Macarena, Hackenberg, Michael, Bragança, José, Calado, Sofia M., Marchal, Juan A., García, María Ángel
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.1/19911
Resumo: Malignant 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.
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spelling Interferon-alpha decreases cancer stem cell properties and modulates exosomes in malignant melanomaInterferon-αMalignant melanomaCancer stem cellsExosomesMetabolomicsBiomarkersMalignant 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.This 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).MDPISapientiaGarcía-Ortega, María BelénAparicio, ErnestoGriñán-Lisón, CarmenJiménez, GemaLópez-Ruiz, ElenaPalacios, José LuisRuiz-Alcalá, GloriaAlba, CristinaMartínez, AntonioBoulaiz, HouriaPerán, MacarenaHackenberg, MichaelBragança, JoséCalado, Sofia M.Marchal, Juan A.García, María Ángel2023-08-01T15:31:24Z2023-07-182023-07-28T12:21:52Z2023-07-18T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/19911engCancers 15 (14): 3666 (2023)2072-669410.3390/cancers15143666info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-08-09T02:01:18Zoai:sapientia.ualg.pt:10400.1/19911Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:10:26.474019Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Interferon-alpha decreases cancer stem cell properties and modulates exosomes in malignant melanoma
title Interferon-alpha decreases cancer stem cell properties and modulates exosomes in malignant melanoma
spellingShingle Interferon-alpha decreases cancer stem cell properties and modulates exosomes in malignant melanoma
García-Ortega, María Belén
Interferon-α
Malignant melanoma
Cancer stem cells
Exosomes
Metabolomics
Biomarkers
title_short Interferon-alpha decreases cancer stem cell properties and modulates exosomes in malignant melanoma
title_full Interferon-alpha decreases cancer stem cell properties and modulates exosomes in malignant melanoma
title_fullStr Interferon-alpha decreases cancer stem cell properties and modulates exosomes in malignant melanoma
title_full_unstemmed Interferon-alpha decreases cancer stem cell properties and modulates exosomes in malignant melanoma
title_sort Interferon-alpha decreases cancer stem cell properties and modulates exosomes in malignant melanoma
author García-Ortega, María Belén
author_facet García-Ortega, María Belén
Aparicio, Ernesto
Griñán-Lisón, Carmen
Jiménez, Gema
López-Ruiz, Elena
Palacios, José Luis
Ruiz-Alcalá, Gloria
Alba, Cristina
Martínez, Antonio
Boulaiz, Houria
Perán, Macarena
Hackenberg, Michael
Bragança, José
Calado, Sofia M.
Marchal, Juan A.
García, María Ángel
author_role author
author2 Aparicio, Ernesto
Griñán-Lisón, Carmen
Jiménez, Gema
López-Ruiz, Elena
Palacios, José Luis
Ruiz-Alcalá, Gloria
Alba, Cristina
Martínez, Antonio
Boulaiz, Houria
Perán, Macarena
Hackenberg, Michael
Bragança, José
Calado, Sofia M.
Marchal, Juan A.
García, María Ángel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Sapientia
dc.contributor.author.fl_str_mv García-Ortega, María Belén
Aparicio, Ernesto
Griñán-Lisón, Carmen
Jiménez, Gema
López-Ruiz, Elena
Palacios, José Luis
Ruiz-Alcalá, Gloria
Alba, Cristina
Martínez, Antonio
Boulaiz, Houria
Perán, Macarena
Hackenberg, Michael
Bragança, José
Calado, Sofia M.
Marchal, Juan A.
García, María Ángel
dc.subject.por.fl_str_mv Interferon-α
Malignant melanoma
Cancer stem cells
Exosomes
Metabolomics
Biomarkers
topic Interferon-α
Malignant melanoma
Cancer stem cells
Exosomes
Metabolomics
Biomarkers
description Malignant 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.
publishDate 2023
dc.date.none.fl_str_mv 2023-08-01T15:31:24Z
2023-07-18
2023-07-28T12:21:52Z
2023-07-18T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.1/19911
url http://hdl.handle.net/10400.1/19911
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Cancers 15 (14): 3666 (2023)
2072-6694
10.3390/cancers15143666
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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