Il27rα deficiency alters endothelial cell function and subverts tumor angiogenesis in mammary carcinoma

IL-27 regulates inflammatory diseases by exerting a pleiotropic impact on immune cells. In cancer, IL-27 restricts tumor growth by acting on tumor cells directly, while its role in the tumor microenvironment is still con
IL-27 regulates inflammatory diseases by exerting a pleiotropic impact on immune cells. In cancer, IL-27 restricts tumor growth by acting on tumor cells directly, while its role in the tumor microenvironment is still controversially discussed. To explore IL-27 signaling in the tumor stroma, we used a mammary carcinoma syngraft approach in IL27Rα-deficient mice. Tumor growth in animals lacking IL27Rα was markedly reduced. We noticed a decrease in immune cell infiltrates, enhanced tumor cell death, and fibroblast accumulation. However, most striking changes pertain the tumor vasculature. Tumors in IL27Rα-deficient mice were unable to form functional vessels. Blocking IL-27-STAT1 signaling in endothelial cells in vitro provoked an overshooting migration/sprouting of endothelial cells. Apparently, the lack of the IL-27 receptor caused endothelial cell hyper-activation via STAT1 that limited vessel maturation. Our data reveal a so far unappreciated role of IL-27 in endothelial cells with importance in pathological vessel formation.
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Metadaten
Author:Annika F. Fink, Giorgia Ciliberti, Rüdiger Popp, Evelyn Sirait-Fischer, Ann-Christin Frank, Ingrid Fleming, Divya Sekar, Andreas Weigert, Bernhard Brüne
URN:urn:nbn:de:hebis:30:3-519977
DOI:http://dx.doi.org/10.3389/fonc.2019.01022
ISSN:2234-943X
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=31637217
Parent Title (English):Frontiers in oncology
Publisher:Frontiers Media
Place of publication:Lausanne
Contributor(s):Laurence A. Marchat
Document Type:Article
Language:English
Year of Completion:2019
Date of first Publication:2019/10/04
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/01/06
Tag:IL-27 cytokine; cytokine, angiogenesis; endothelial cell; mammary cancer
Volume:9
Issue:Art. 1022
Pagenumber:14
First Page:1
Last Page:14
Note:
Copyright © 2019 Fink, Ciliberti, Popp, Sirait-Fischer, Frank, Fleming, Sekar, Weigert and Brüne. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
HeBIS PPN:458140759
Institutes:Medizin
Sonderforschungsbereiche / Forschungskollegs
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Open-Access-Publikationsfonds:Medizin
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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