2026-06-14T03:51:48Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/138162024-11-28T15:54:22Zcom_20.500.12105_2173com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19597col_20.500.12105_16938
Repisalud
author
Cerezo-Wallis, Daniela
author
Mucientes, Cynthia
author
Calvo, Tonantzin G
author
Cañón, Estela
author
Alonso-Curbelo, Direna
author
Ibarz, Nuria
author
Muñoz, Javier
author
Rodriguez-Peralto, José L
author
Ortiz-Romero, Pablo
author
Soengas, MS
author
Ortega Jimenez, Sagrario
author
Olmeda, David
funder
Asociación Española Contra el Cáncer
funder
Fundación La Caixa
funder
Melanoma Research Alliance
funder
Instituto de Salud Carlos III
funder
Fundación BBVA
funder
Ministerio de Economía, Industria y Competitividad (España)
2022-03-24T13:45:45Z
2022-03-24T13:45:45Z
2021-12-07
EMBO Mol Med . 2021;13(12):e12924
10.15252/emmm.202012924
1757-4684
EMBO molecular medicine
34762341
http://hdl.handle.net/20.500.12105/13816
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.
eng
Live imaging of neolymphangiogenesis identifies acute antimetastatic roles of dsRNA mimics.
journal article
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