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Interleukin-11 is a Marker for Both Cancer- and Inflammation-Associated Fibroblasts that Contribute to Colorectal Cancer Progression

Interleukin-11 is a Marker for Both Cancer- and Inflammation-Associated Fibroblasts that Contribute to Colorectal Cancer Progression

Authors :
Hiroyasu Nakano
Yutaka Deguchi
Eri Nakamura
Masato Ohtsuka
Kazutoshi Shibuya
Takashi Nishina
Hideo Yagita
Daisuke Ohshima
Mizuho Nakayama
Mika Kawauchi
Wakami Takeda
Norihiro Tada
Mizuho Hasegawa
Chiharu Nishiyama
Naohiro Inohara
Satomi Adachi-Akahane
Masanobu Oshima
Soh Yamazaki
Yuko Kojima
Tetuo Mikami
Publication Year :
2020
Publisher :
Cold Spring Harbor Laboratory, 2020.

Abstract

SUMMARYInterleukin (IL)-11 is a member of the IL-6 family of cytokines and involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generated Il11 reporter mice. IL-11+ cells appeared in the colon of three murine tumor models, and a murine acute colitis model. Il11ra1 or Il11 deletion attenuated the development of colitis-associated colorectal cancer. IL-11+ cells expressed fibroblast markers, and genes associated with cell proliferation and tissue repair. IL-11 induced STAT3 phosphorylation in colonic fibroblasts, suggesting the activation of IL-11+ fibroblasts. Analysis using the human cancer database revealed that genes enriched in IL-11+ fibroblasts were elevated in human colorectal cancer, and correlated with reduced disease-free survival. Together, our results suggested that tumor cells induced IL-11+ fibroblasts, and that a feed-forward loop between IL-11 and IL-11+ fibroblasts might contribute to tumor development.

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....a1e3cada8a9e1f5b821661058025f529
Full Text :
https://doi.org/10.1101/2020.01.25.919795