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In vivo inhibition of c-MYC in myeloid cells impairs tumor-associated macrophage maturation and pro-tumoral activities

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dc.contributor.authorPello, Oscar M
dc.contributor.authorChevre, Raphael
dc.contributor.authorLaoui, Damya
dc.contributor.authorDe Juan, Alba
dc.contributor.authorLolo, Fidel Nicolas
dc.contributor.authorAndres-Manzano, Maria J.
dc.contributor.authorSerrano, Manuel
dc.contributor.authorVan Ginderachter, Jo A
dc.contributor.authorAndres, Vicente
dc.contributor.funderMinisterio de Ciencia e Innovación (España)
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
dc.contributor.funderInstituto de Salud Carlos III
dc.contributor.funderMinisterio de Economía y Competitividad (España)
dc.contributor.funderUnión Europea. Comisión Europea
dc.contributor.funderFundación ProCNIC
dc.date.accessioned2019-05-23T10:06:18Z
dc.date.available2019-05-23T10:06:18Z
dc.date.issued2012
dc.description.abstractAlthough tumor-associated macrophages (TAMs) are involved in tumor growth and metastasis, the mechanisms controlling their pro-tumoral activities remain largely unknown. The transcription factor c-MYC has been recently shown to regulate in vitro human macrophage polarization and be expressed in macrophages infiltrating human tumors. In this study, we exploited the predominant expression of LysM in myeloid cells to generate c-Myc(fl/fl) LysM(cre/+) mice, which lack c-Myc in macrophages, to investigate the role of macrophage c-MYC expression in cancer. Under steady-state conditions, immune system parameters in c-Myc(fl/fl) LysM(cre/+) mice appeared normal, including the abundance of different subsets of bone marrow hematopoietic stem cells, precursors and circulating cells, macrophage density, and immune organ structure. In a model of melanoma, however, TAMs lacking c-Myc displayed a delay in maturation and showed an attenuation of pro-tumoral functions (e.g., reduced expression of VEGF, MMP9, and HIF1α) that was associated with impaired tissue remodeling and angiogenesis and limited tumor growth in c-Myc(fl/fl) LysM(cre/+) mice. Macrophage c-Myc deletion also diminished fibrosarcoma growth. These data identify c-Myc as a positive regulator of the pro-tumoral program of TAMs and suggest c-Myc inactivation as an attractive target for anti-cancer therapy.es_ES
dc.description.peerreviewedSíes_ES
dc.description.sponsorshipThe V.A. lab is supported by grant SAF2010-16044 from the Spanish Ministry of Science and Innovation (MICINN) and the European Regional Development Fund, grant RD06/0014/0021 (RECAVA, Instituto de Salud Carlos III), and the Dr. Leon Dumont Prize 2010 (Belgian Society of Cardiology). O.M.P. holds a Juan de la Cierva contract from the Spanish Ministry of Economy and Competition (MINECO). The CNIC is supported by the MINECO and the Pro-CNICes_ES
dc.format.number9es_ES
dc.format.pagee45399es_ES
dc.format.volume7es_ES
dc.identifier.citationPLoS One. 2012; 7(9):e45399es_ES
dc.identifier.doi10.1371/journal.pone.0045399es_ES
dc.identifier.e-issn1932-6203es_ES
dc.identifier.issn1932-6203es_ES
dc.identifier.journalPloS onees_ES
dc.identifier.pubmedID23028984es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7665
dc.language.isoenges_ES
dc.publisherPublic Library of Science (PLOS)es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/303850/EUes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2010-16044es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD06/0014/0021es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/AF2010-16044es_ES
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pone.0045399es_ES
dc.repisalud.institucionCNICes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Fisiopatología Cardiovascular Molecular y Genéticaes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshAnimalses_ES
dc.subject.meshCell Line, Tumores_ES
dc.subject.meshFemalees_ES
dc.subject.meshFlow Cytometryes_ES
dc.subject.meshImmunohistochemistryes_ES
dc.subject.meshMacrophageses_ES
dc.subject.meshMalees_ES
dc.subject.meshMicees_ES
dc.subject.meshMicroscopy, Confocales_ES
dc.subject.meshMyeloid Cellses_ES
dc.subject.meshProto-Oncogene Proteins c-myces_ES
dc.subject.meshReal-Time Polymerase Chain Reactiones_ES
dc.titleIn vivo inhibition of c-MYC in myeloid cells impairs tumor-associated macrophage maturation and pro-tumoral activitieses_ES
dc.typejournal articlees_ES
dc.type.hasVersionVoRes_ES
dspace.entity.typePublication
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