Interleukin-13 and its signaling pathway is associated with obesity-related colorectal tumorigenesis

Shimpei Matsui, Koji Okabayashi, Masashi Tsuruta, Kohei Shigeta, Ryo Seishima, Takashi Ishida, Takayuki Kondo, Yoshiyuki Suzuki, Hirotoshi Hasegawa, Masayuki Shimoda, Shinya Sugimoto, Toshiro Sato, Yuukou Kitagawa

Research output: Contribution to journalArticle

Abstract

The incidence of colorectal cancer (CRC) has been on the rise, which is linked to the increasing prevalence of obesity, based on global epidemiological evidence. Although chronic inflammation is implicated in tumor development, the mechanisms underlying obesity-associated CRC remain unknown. Here, we sought to identify the inflammatory cytokines and their roles in obesity-related colorectal tumorigenesis using cytokine array analyses in a mouse model. Colorectal tumorigenesis was induced through i.p. injection of azoxymethane once a week for 6 weeks in 6-week-old female WT C57Black/6J mice and the obesity diabetes model mouse KK/TaJcl, KK-Ay/TaJcl. The formation of aberrant crypt foci and colorectal tumors were more frequent in obese mice compared with WT mice, and both serum interleukin (IL)-13 and IL-13 receptor (R) expression in the normal intestinal mucosal epithelium were significantly increased in the obese mice. Furthermore, addition of IL-13 to a human CRC cell line and a human colon organoid culture altered the phenotype of intestinal epithelial cells. Knockdown experiments further revealed that IL-13Rα1 dominantly induced mucosal proliferation. Collectively, These results suggest an association between anti-inflammatory cytokines and colorectal carcinogenesis, and provide new research directions for cancer prevention strategies. In particular, inflammation provoked by obesity, notably by increased expression of the cytokine IL-13, could play an important role in the carcinogenesis of obesity-related CRC.

Original languageEnglish
Pages (from-to)2156-2165
Number of pages10
JournalCancer science
Volume110
Issue number7
DOIs
Publication statusPublished - 2019 Jul 1

Fingerprint

Interleukin-13
Carcinogenesis
Obesity
Colorectal Neoplasms
Cytokines
Obese Mice
Interleukin-13 Receptors
Organoids
Aberrant Crypt Foci
Azoxymethane
Inflammation
Interleukins
Intestinal Mucosa
Neoplasms
Colon
Anti-Inflammatory Agents
Epithelial Cells
Phenotype
Cell Line
Injections

Keywords

  • carcinogenesis
  • colorectal cancer
  • cytokine
  • IL-13
  • obesity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Interleukin-13 and its signaling pathway is associated with obesity-related colorectal tumorigenesis. / Matsui, Shimpei; Okabayashi, Koji; Tsuruta, Masashi; Shigeta, Kohei; Seishima, Ryo; Ishida, Takashi; Kondo, Takayuki; Suzuki, Yoshiyuki; Hasegawa, Hirotoshi; Shimoda, Masayuki; Sugimoto, Shinya; Sato, Toshiro; Kitagawa, Yuukou.

In: Cancer science, Vol. 110, No. 7, 01.07.2019, p. 2156-2165.

Research output: Contribution to journalArticle

@article{d426ce0a80bf46a399df20098db2e252,
title = "Interleukin-13 and its signaling pathway is associated with obesity-related colorectal tumorigenesis",
abstract = "The incidence of colorectal cancer (CRC) has been on the rise, which is linked to the increasing prevalence of obesity, based on global epidemiological evidence. Although chronic inflammation is implicated in tumor development, the mechanisms underlying obesity-associated CRC remain unknown. Here, we sought to identify the inflammatory cytokines and their roles in obesity-related colorectal tumorigenesis using cytokine array analyses in a mouse model. Colorectal tumorigenesis was induced through i.p. injection of azoxymethane once a week for 6 weeks in 6-week-old female WT C57Black/6J mice and the obesity diabetes model mouse KK/TaJcl, KK-Ay/TaJcl. The formation of aberrant crypt foci and colorectal tumors were more frequent in obese mice compared with WT mice, and both serum interleukin (IL)-13 and IL-13 receptor (R) expression in the normal intestinal mucosal epithelium were significantly increased in the obese mice. Furthermore, addition of IL-13 to a human CRC cell line and a human colon organoid culture altered the phenotype of intestinal epithelial cells. Knockdown experiments further revealed that IL-13Rα1 dominantly induced mucosal proliferation. Collectively, These results suggest an association between anti-inflammatory cytokines and colorectal carcinogenesis, and provide new research directions for cancer prevention strategies. In particular, inflammation provoked by obesity, notably by increased expression of the cytokine IL-13, could play an important role in the carcinogenesis of obesity-related CRC.",
keywords = "carcinogenesis, colorectal cancer, cytokine, IL-13, obesity",
author = "Shimpei Matsui and Koji Okabayashi and Masashi Tsuruta and Kohei Shigeta and Ryo Seishima and Takashi Ishida and Takayuki Kondo and Yoshiyuki Suzuki and Hirotoshi Hasegawa and Masayuki Shimoda and Shinya Sugimoto and Toshiro Sato and Yuukou Kitagawa",
year = "2019",
month = "7",
day = "1",
doi = "10.1111/cas.14066",
language = "English",
volume = "110",
pages = "2156--2165",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "7",

}

TY - JOUR

T1 - Interleukin-13 and its signaling pathway is associated with obesity-related colorectal tumorigenesis

AU - Matsui, Shimpei

AU - Okabayashi, Koji

AU - Tsuruta, Masashi

AU - Shigeta, Kohei

AU - Seishima, Ryo

AU - Ishida, Takashi

AU - Kondo, Takayuki

AU - Suzuki, Yoshiyuki

AU - Hasegawa, Hirotoshi

AU - Shimoda, Masayuki

AU - Sugimoto, Shinya

AU - Sato, Toshiro

AU - Kitagawa, Yuukou

PY - 2019/7/1

Y1 - 2019/7/1

N2 - The incidence of colorectal cancer (CRC) has been on the rise, which is linked to the increasing prevalence of obesity, based on global epidemiological evidence. Although chronic inflammation is implicated in tumor development, the mechanisms underlying obesity-associated CRC remain unknown. Here, we sought to identify the inflammatory cytokines and their roles in obesity-related colorectal tumorigenesis using cytokine array analyses in a mouse model. Colorectal tumorigenesis was induced through i.p. injection of azoxymethane once a week for 6 weeks in 6-week-old female WT C57Black/6J mice and the obesity diabetes model mouse KK/TaJcl, KK-Ay/TaJcl. The formation of aberrant crypt foci and colorectal tumors were more frequent in obese mice compared with WT mice, and both serum interleukin (IL)-13 and IL-13 receptor (R) expression in the normal intestinal mucosal epithelium were significantly increased in the obese mice. Furthermore, addition of IL-13 to a human CRC cell line and a human colon organoid culture altered the phenotype of intestinal epithelial cells. Knockdown experiments further revealed that IL-13Rα1 dominantly induced mucosal proliferation. Collectively, These results suggest an association between anti-inflammatory cytokines and colorectal carcinogenesis, and provide new research directions for cancer prevention strategies. In particular, inflammation provoked by obesity, notably by increased expression of the cytokine IL-13, could play an important role in the carcinogenesis of obesity-related CRC.

AB - The incidence of colorectal cancer (CRC) has been on the rise, which is linked to the increasing prevalence of obesity, based on global epidemiological evidence. Although chronic inflammation is implicated in tumor development, the mechanisms underlying obesity-associated CRC remain unknown. Here, we sought to identify the inflammatory cytokines and their roles in obesity-related colorectal tumorigenesis using cytokine array analyses in a mouse model. Colorectal tumorigenesis was induced through i.p. injection of azoxymethane once a week for 6 weeks in 6-week-old female WT C57Black/6J mice and the obesity diabetes model mouse KK/TaJcl, KK-Ay/TaJcl. The formation of aberrant crypt foci and colorectal tumors were more frequent in obese mice compared with WT mice, and both serum interleukin (IL)-13 and IL-13 receptor (R) expression in the normal intestinal mucosal epithelium were significantly increased in the obese mice. Furthermore, addition of IL-13 to a human CRC cell line and a human colon organoid culture altered the phenotype of intestinal epithelial cells. Knockdown experiments further revealed that IL-13Rα1 dominantly induced mucosal proliferation. Collectively, These results suggest an association between anti-inflammatory cytokines and colorectal carcinogenesis, and provide new research directions for cancer prevention strategies. In particular, inflammation provoked by obesity, notably by increased expression of the cytokine IL-13, could play an important role in the carcinogenesis of obesity-related CRC.

KW - carcinogenesis

KW - colorectal cancer

KW - cytokine

KW - IL-13

KW - obesity

UR - http://www.scopus.com/inward/record.url?scp=85068549884&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068549884&partnerID=8YFLogxK

U2 - 10.1111/cas.14066

DO - 10.1111/cas.14066

M3 - Article

C2 - 31099450

AN - SCOPUS:85068549884

VL - 110

SP - 2156

EP - 2165

JO - Cancer Science

JF - Cancer Science

SN - 1347-9032

IS - 7

ER -