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World J Clin Cases. Jan 7, 2022; 10(1): 23-34
Published online Jan 7, 2022. doi: 10.12998/wjcc.v10.i1.23
Paradoxical role of interleukin-33/suppressor of tumorigenicity 2 in colorectal carcinogenesis: Progress and therapeutic potential
Fang Huang, Wan-Yuan Chen, Jie Ma, Xiang-Lei He, Jian-Wei Wang
Fang Huang, Wan-Yuan Chen, Jie Ma, Xiang-Lei He, Jian-Wei Wang, Department of Pathology, Laboratory Medicine Center, Zhejiang Provincial Peoples’ Hospital, Peoples’ Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
Fang Huang, Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Peoples’ Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
Author contributions: Huang F and Wang JW contributed to the conception and design of the paper, literature review; Huang F, Chen WY, and Ma J searched the literature and wrote the paper; Huang F drew the picture and table, and Huang F, He XL and Wang JW revised the paper.
Supported by Natural Science Foundation of China, No. 81803069; Zhejiang Medical Technology Plan Project, No. 2019RC007, No. 2019KY007 and No. 2021KY047; and Funds of Science Technology Department of Zhejiang Province, No. LGF21H160033.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jian-Wei Wang, MD, Assistant Professor, Department of Pathology, Laboratory Medicine Center, Zhejiang Provincial Peoples’ Hospital, Peoples’ Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou 310014, Zhejiang Province, China. wangjianwei2002@126.com
Received: April 26, 2021
Peer-review started: April 26, 2021
First decision: May 27, 2021
Revised: June 14, 2021
Accepted: August 24, 2021
Article in press: August 24, 2021
Published online: January 7, 2022
Processing time: 247 Days and 23.4 Hours
Abstract

Colorectal cancer (CRC) is presently the second most prevalent global mortality-inducing cancer. CRC carcinogenesis is a multifactorial process involving internal genetic mutations and the external environment. In addition, non-neoplastic cell activities within tumor microenvironments for CRC development have been established. However, interleukin (IL)-33, secreted by such cell types, plays a pivotal role in cancer progression due to interaction with cellular constituents within the tumor-inflammation microenvironment. IL-33 belongs to the IL-1 cytokine family and acts as binding attachments for the suppressor of tumorigenicity (ST)2 receptor. Therefore, how to coordinate tumor microenvironment, design and optimize treatment strategies suitable for CRC, based on IL-33/ST2 signal is a challenge. Even though it has established influences upon immunity-linked conditions, IL-33 effects on CRC progression and prevention and related mechanisms are still controversial. Our review depicts controversial activities for IL-33/ST2 within carcinogenesis and cancer prevention. Moreover, IL-33/ST2 signaling is a potential therapeutic target for CRC.

Keywords: Interleukin 33; Suppressor of tumorigenicity 2 signaling; Tumor microenvironment; Conventional therapies; Colorectal cancer

Core tip: Interleukin (IL)-33 belongs to the IL-1 cytokine family and binds to the suppressor of tumorigenicity (ST)2 receptor. IL-33 plays a key role in cancer progression due to interaction with cellular components in the inflammatory microenvironment of tumors. Therefore, it is a challenge to design and optimize treatment strategies suitable for colorectal cancer (CRC) based on IL-33/ST2 signaling to coordinate the tumor microenvironment. IL-33 also has effects on CRC prevention. These findings implicate multifaceted roles of IL-33 in cancer treatment.