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dc.contributor.author | Cerezo-Wallis, Daniela | |
dc.contributor.author | Mucientes, Cynthia | |
dc.contributor.author | Calvo, Tonantzin G | |
dc.contributor.author | Cañón, Estela | |
dc.contributor.author | Alonso-Curbelo, Direna | |
dc.contributor.author | Ibarz, Nuria | |
dc.contributor.author | Muñoz, Javier | |
dc.contributor.author | Rodriguez-Peralto, José L | |
dc.contributor.author | Ortiz-Romero, Pablo | |
dc.contributor.author | Soengas, MS | |
dc.contributor.author | Ortega Jimenez, Sagrario | |
dc.contributor.author | Olmeda, David | |
dc.date.accessioned | 2022-03-24T13:45:45Z | |
dc.date.available | 2022-03-24T13:45:45Z | |
dc.date.issued | 2021-12-07 | |
dc.identifier.citation | EMBO Mol Med . 2021;13(12):e12924 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/13816 | |
dc.description.abstract | Long-range communication between tumor cells and the lymphatic vasculature defines competency for metastasis in different cancer types, particularly in melanoma. Nevertheless, the discovery of selective blockers of lymphovascular niches has been compromised by the paucity of experimental systems for whole-body analyses of tumor progression. Here, we exploit immunocompetent and immunodeficient mouse models for live imaging of Vegfr3-driven neolymphangiogenesis, as a versatile platform for drug screening in vivo. Spatiotemporal analyses of autochthonous melanomas and patient-derived xenografts identified double-stranded RNA mimics (dsRNA nanoplexes) as potent inhibitors of neolymphangiogenesis, metastasis, and post-surgical disease relapse. Mechanistically, dsRNA nanoplexes were found to exert a rapid dual action in tumor cells and in their associated lymphatic vasculature, involving the transcriptional repression of the lymphatic drivers Midkine and Vegfr3, respectively. This suppressive function was mediated by a cell-autonomous type I interferon signaling and was not shared by FDA-approved antimelanoma treatments. These results reveal an alternative strategy for targeting the tumor cell-lymphatic crosstalk and underscore the power of Vegfr3-lymphoreporters for pharmacological testing in otherwise aggressive cancers. | es_ES |
dc.description.sponsorship | The authors thank previous and present colleagues in the CNIO Melanoma Group, particularly Damia Tormo and Lisa Osterloh for help and support at the initial stages of this study; Jose A Esteban (CSIC-UAM) for critical reading of this manuscript; Lionel Larue (INSERM; France) and Martin McMahon (Hunstman Cancer Center, USA) for the Tyr:CreERT2 and BrafCA mouse strains, respectively; and Ignacio Melero at Hospital Clinico, Pamplona, Spain, for Ifnar1-deficient mice. The authors thank Isabel Blanco, Soraya Ruiz, and Virginia Granda (CNIO-Animal Facility Unit), Diego Megias (CNIO-Confocal Unit), and Eduardo Jose Caleiras and Patricia Gonzalez (CNIO-Histopathology Unit) for technical assistance. M.S.S. is funded by grants from the Spanish Ministry of Economy and Innovation (SAF2017-89533-R), the Asociacion Espanola Contra el Cancer (AECC), Fundacion La Caixa, and an Established Investigator Award by the Melanoma Research Alliance (MRA). D.O. is funded by grants from the Spanish Ministry of Health (AES-PIS PI18/1057) and "Beca Leonardo a Investigadores y Creadores Culturales 2018 de la Fundacion BBVA". The CNIO Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019. S.O. is also supported by a grant from the Spanish Ministry of Economy, Industry and Competitiveness (BFU2015-71376-R). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject.mesh | Melanoma | es_ES |
dc.subject.mesh | RNA, Double-Stranded | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Mice, Nude | es_ES |
dc.subject.mesh | Signal Transduction | es_ES |
dc.title | Live imaging of neolymphangiogenesis identifies acute antimetastatic roles of dsRNA mimics. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-NoComercial-CompartirIgual 4.0 Internacional | * |
dc.identifier.pubmedID | 34762341 | es_ES |
dc.format.volume | 13 | es_ES |
dc.format.number | 12 | es_ES |
dc.format.page | e12924 | es_ES |
dc.identifier.doi | 10.15252/emmm.202012924 | es_ES |
dc.contributor.funder | Asociación Española Contra el Cáncer | es_ES |
dc.contributor.funder | Fundación La Caixa | es_ES |
dc.contributor.funder | Melanoma Research Alliance | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | Fundación BBVA | es_ES |
dc.contributor.funder | Ministerio de Economía, Industria y Competitividad (España) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1757-4684 | es_ES |
dc.relation.publisherversion | https://doi.org/10.15252/emmm.202012924. | es_ES |
dc.identifier.journal | EMBO molecular medicine | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Grupos de investigación::Grupo de Melanoma | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/SAF2017-89533-R | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/AES-PIS PI18/1057 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/BFU2015-71376-R | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ PT17/0019 | es_ES |