Header

UZH-Logo

Maintenance Infos

The IL-33/ST2 pathway contributes to intestinal tumorigenesis in humans and mice


Abstract

Colorectal cancer (CRC) develops through a multistep process and is modulated by inflammation. However, the inflammatory pathways that support intestinal tumors at different stages remain incompletely understood. Interleukin (IL)-33 signaling plays a role in intestinal inflammation, yet its contribution to the pathogenesis of CRC is unknown. Using immunohistochemistry on 713 resected human CRC specimens, we show here that IL-33 and its receptor ST2 are expressed in low-grade and early-stage human CRCs, and to a lesser extent in higher-grade and more advanced-stage tumors. In a mouse model of CRC, ST2-deficiency protects from tumor development. Moreover, bone marrow (BM) chimera studies indicate that engagement of the IL-33/ST2 pathway on both the radio-resistant and radio-sensitive compartment is essential for CRC development. Mechanistically, activation of IL-33/ST2 signaling compromises the integrity of the intestinal barrier and triggers the production of pro-tumorigenic IL-6 by immune cells. Together, this data reveals a tumor-promoting role of IL-33/ST2 signaling in CRC.

Abstract

Colorectal cancer (CRC) develops through a multistep process and is modulated by inflammation. However, the inflammatory pathways that support intestinal tumors at different stages remain incompletely understood. Interleukin (IL)-33 signaling plays a role in intestinal inflammation, yet its contribution to the pathogenesis of CRC is unknown. Using immunohistochemistry on 713 resected human CRC specimens, we show here that IL-33 and its receptor ST2 are expressed in low-grade and early-stage human CRCs, and to a lesser extent in higher-grade and more advanced-stage tumors. In a mouse model of CRC, ST2-deficiency protects from tumor development. Moreover, bone marrow (BM) chimera studies indicate that engagement of the IL-33/ST2 pathway on both the radio-resistant and radio-sensitive compartment is essential for CRC development. Mechanistically, activation of IL-33/ST2 signaling compromises the integrity of the intestinal barrier and triggers the production of pro-tumorigenic IL-6 by immune cells. Together, this data reveals a tumor-promoting role of IL-33/ST2 signaling in CRC.

Statistics

Citations

5 citations in Web of Science®
8 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

29 downloads since deposited on 23 May 2016
12 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Colorectal cancer, IL-33, inflammation, mouse model, ST2, tissue microarray, tumor microenvironment
Language:English
Date:2016
Deposited On:23 May 2016 14:25
Last Modified:06 Aug 2017 00:31
Publisher:Landes Bioscience
ISSN:2162-4011
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1080/2162402X.2015.1062966
PubMed ID:26942077

Download

Download PDF  'The IL-33/ST2 pathway contributes to intestinal tumorigenesis in humans and mice'.
Preview
Content: Published Version
Language: English
Filetype: PDF
Size: 1MB
View at publisher
Licence: Creative Commons: Attribution-NonCommercial 3.0 Unported (CC BY-NC 3.0)