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dc.contributor.authorPalacios-Ferrer, José Luis
dc.contributor.authorGarcía-Ortega, María Belén
dc.contributor.authorGallardo-Gómez, María
dc.contributor.authorGarcía, María Ángel
dc.contributor.authorDíaz, Caridad
dc.contributor.authorBoulaiz, Houria
dc.contributor.authorValdivia, Javier
dc.contributor.authorJurado, José Miguel
dc.contributor.authorAlmazan-Fernandez, Francisco M
dc.contributor.authorArias-Santiago, Salvador
dc.contributor.authorAmezcua, Víctor
dc.contributor.authorPeinado, Héctor
dc.contributor.authorVicente, Francisca
dc.contributor.authorPérez Del Palacio, José
dc.contributor.authorMarchal, Juan A
dc.contributor.authorPeinado Selgas, Hector 
dc.date.accessioned2021-03-31T11:34:10Z
dc.date.available2021-03-31T11:34:10Z
dc.date.issued2021-02-15
dc.identifier.citationMol Oncol. 2021;15(2):407-428.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/12497
dc.description.abstractMalignant melanoma (MM) is the most aggressive and life-threatening form of skin cancer. It is characterized by an extraordinary metastasis capacity and chemotherapy resistance, mainly due to melanoma cancer stem cells (CSCs). To date, there are no suitable clinical diagnostic, prognostic or predictive biomarkers for this neoplasia. Therefore, there is an urgent need for new MM biomarkers that enable early diagnosis and effective disease monitoring. Exosomes represent a novel source of biomarkers since they can be easily isolated from different body fluids. In this work, a primary patient-derived MM cell line enriched in CSCs was characterized by assessing the expression of specific markers and their stem-like properties. Exosomes derived from CSCs and serums from patients with MM were characterized, and their metabolomic profile was analysed by high-resolution mass spectrometry (HRMS) following an untargeted approach and applying univariate and multivariate statistical analyses. The aim of this study was to search potential biomarkers for the diagnosis of this disease. Our results showed significant metabolomic differences in exosomes derived from MM CSCs compared with those from differentiated tumour cells and also in serum-derived exosomes from patients with MM compared to those from healthy controls. Interestingly, we identified similarities between structural lipids differentially expressed in CSC-derived exosomes and those derived from patients with MM such as the glycerophosphocholine PC 16:0/0:0. To our knowledge, this is the first metabolomic-based study aimed at characterizing exosomes derived from melanoma CSCs and patients' serum in order to identify potential biomarkers for MM diagnosis. We conclude that metabolomic characterization of CSC-derived exosomes sets an open door to the discovery of clinically useful biomarkers in this neoplasia.es_ES
dc.description.sponsorshipThe authors would like to thank Dr Jaime Lazuen and Dr Gustavo Ortiz from the C.I.C. (University of Granada) for the excellent technical assistance in the cytometry analyses, Dr Juan Felix Lopez (BIONAND) for his assistance and advice on electron immunogold labelling microscopy characterization and Daniel Franco (Fundacion MEDINA) for his technical assistance with LC-HRMS analyses. JLP-F (Ref. FPU15/03682) and MG-G (Ref. FPU15/02350) acknowledge the MICIU for providing a PhD fellowship (FPU). This research was supported by the Ministerio de Ciencia, Innovacion y Universidades (MICIU, project nos. MAT2015-62644.C2.2.R and RTI2018-101309-BC2, FEDER Funds), by the Instituto de Salud Carlos III (PIE16-00045), by Consejeria de Economia, Conocimiento, Empresas y Universidad de la Junta de Andalucia and European Regional Development Fund (ERDF), ref. SOMM17/6109/UGR (UCE-PP2017-3), and by the Chair 'Doctors Galera-Requena in cancer stem cell research' (CMC-CTS963). MEDINA authors disclosed the receipt of financial support from Fundacion MEDINA, a public-private partnership of Merck Sharp and Dohme de Espana S.A./Universidad de Granada/Junta de Andalucia.es_ES
dc.language.isoenges_ES
dc.publisherWiley es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectHEPATOCELULAR CARCINOMAes_ES
dc.subjectTHERAPEUTIC TARGETes_ES
dc.subjectTUMORes_ES
dc.subjectBIOMARKERSes_ES
dc.subjectPLASMAes_ES
dc.subjectMICROVESICLESes_ES
dc.subjectREVEALSes_ES
dc.subjectDISEASEes_ES
dc.titleMetabolomic profile of cancer stem cell-derived exosomes from patients with malignant melanoma.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID33052601es_ES
dc.format.volume15es_ES
dc.format.number2es_ES
dc.format.page407-428es_ES
dc.identifier.doi10.1002/1878-0261.12823es_ES
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (España) 
dc.contributor.funderUnión Europea. Comisión Europea 
dc.contributor.funderRegional Government of Andalusia (España) 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1878-0261es_ES
dc.relation.publisherversionhttps://doi.org/10.1002/1878-0261.12823.es_ES
dc.identifier.journalMolecular oncologyes_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Microambiente y Metástasises_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FPU15/03682es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FPU15/02350es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PIE16-00045es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/MAT2015-62644.C2.2.Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RTI2018-101309-BC2es_ES
dc.rights.accessRightsopen accesses_ES


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Atribución-NoComercial-CompartirIgual 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Atribución-NoComercial-CompartirIgual 4.0 Internacional