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 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.
Author: | Annika F. FinkGND, Giorgia Ciliberti, Rüdiger Popp, Evelyn Nicole Joy Sirait-FischerORCiDGND, Ann-Christin FrankORCiDGND, Ingrid FlemingORCiDGND, Divya Sekar, Andreas WeigertORCiDGND, Bernhard BrüneORCiD |
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URN: | urn:nbn:de:hebis:30:3-519977 |
DOI: | https://doi.org/10.3389/fonc.2019.01022 |
ISSN: | 2234-943X |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/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 |
Page Number: | 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 / Medizin |
Wissenschaftliche Zentren und koordinierte Programme / Sonderforschungsbereiche / Forschungskollegs | |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Open-Access-Publikationsfonds: | Medizin |
Licence (German): | Creative Commons - Namensnennung 4.0 |