The IL-33/ST2 Pathway Contributes to Intestinal Tumorigenesis in Humans and Mice

Overview

Journal Oncoimmunology

Specialty Allergy & Immunology

Date 2016 Mar 5

PMID 26942077

Citations 53

Authors

Kirsten D Mertz

Lukas F Mager

Marie-Helene Wasmer

Thore Thiesler

Viktor H Koelzer

Giulia Ruzzante

Stefanie Joller

Jenna R Murdoch

Thomas Brummendorf

Vera Genitsch

Alessandro Lugli

Gieri Cathomas

Holger Moch

Achim Weber

Inti Zlobec

Tobias Junt

Philippe Krebs

Affiliations

Soon will be listed here.

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.

Citing Articles

Colorectal Cancer in Correlation With Clinicopathological Variables: The Effects of Hypoxia-Inducible Factor-1 Alfa or the InterLeukin-33 and Vascular Endothelial Growth Factor?.

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IL-33/ST2 Signaling and its Correlation with Macrophage Heterogeneity and Clinicopathologic Features in Human Intrahepatic Cholangiocarcinoma.

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Interleukin-33 as a Potential Therapeutic Target in Gastric Cancer Patients: Current Insights.

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