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Tytuł pozycji:

Live imaging of neolymphangiogenesis identifies acute antimetastatic roles of dsRNA mimics.

Tytuł:
Live imaging of neolymphangiogenesis identifies acute antimetastatic roles of dsRNA mimics.
Autorzy:
Olmeda D; Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Cerezo-Wallis D; Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Mucientes C; Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Calvo TG; Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Cañón E; Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Alonso-Curbelo D; Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Ibarz N; Proteomics Unit, Biotechnology Programme, ProteoRed-ISCIII, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Muñoz J; Proteomics Unit, Biotechnology Programme, ProteoRed-ISCIII, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Rodriguez-Peralto JL; Instituto de Investigación i+12, Hospital 12 de Octubre, Universidad Complutense Madrid Medical School, Madrid, Spain.
Ortiz-Romero P; Department of Dermatology, Hospital 12 de Octubre, Universidad Complutense Madrid Medical School, Madrid, Spain.
Ortega S; Mouse Genome Editing Core Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Soengas MS; Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Źródło:
EMBO molecular medicine [EMBO Mol Med] 2021 Dec 07; Vol. 13 (12), pp. e12924. Date of Electronic Publication: 2021 Nov 11.
Typ publikacji:
Journal Article; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: Chichester, West Sussex : Wiley-Blackwell
MeSH Terms:
Melanoma*/drug therapy
Melanoma*/pathology
RNA, Double-Stranded*
Animals ; Humans ; Mice ; Mice, Nude ; Signal Transduction
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Contributed Indexing:
Keywords: GEMM melanoma models; dsRNA nanoplexes; midkine; neolymphangiogenesis; premetastatic niche
Substance Nomenclature:
0 (RNA, Double-Stranded)
Entry Date(s):
Date Created: 20211111 Date Completed: 20220311 Latest Revision: 20231108
Update Code:
20240105
PubMed Central ID:
PMC8649872
DOI:
10.15252/emmm.202012924
PMID:
34762341
Czasopismo naukowe
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.
(© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

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