Interferon-alpha decreases cancer stem cell properties and modulates exosomes in malignant melanoma
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , , , , , , , , |
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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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) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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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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