Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer

Takashi Nishina (), Yutaka Deguchi, Daisuke Ohshima, Wakami Takeda, Masato Ohtsuka, Shigeyuki Shichino, Satoshi Ueha, Soh Yamazaki, Mika Kawauchi, Eri Nakamura, Chiharu Nishiyama, Yuko Kojima, Satomi Adachi-Akahane, Mizuho Hasegawa, Mizuho Nakayama, Masanobu Oshima, Hideo Yagita, Kazutoshi Shibuya, Tetuo Mikami, Naohiro Inohara, Kouji Matsushima, Norihiro Tada and Hiroyasu Nakano ()
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Takashi Nishina: Toho University School of Medicine
Yutaka Deguchi: Toho University School of Medicine
Daisuke Ohshima: Toho University School of Medicine
Wakami Takeda: Toho University School of Medicine
Masato Ohtsuka: Tokai University
Shigeyuki Shichino: Tokyo University of Science
Satoshi Ueha: Tokyo University of Science
Soh Yamazaki: Toho University School of Medicine
Mika Kawauchi: Toho University School of Medicine
Eri Nakamura: Juntendo University School of Medicine
Chiharu Nishiyama: Tokyo University of Science
Yuko Kojima: Juntendo University Graduate School of Medicine
Satomi Adachi-Akahane: Toho University School of Medicine
Mizuho Hasegawa: University of Michigan Medical School
Mizuho Nakayama: Kanazawa University
Masanobu Oshima: Kanazawa University
Hideo Yagita: Juntendo University Graduate School of Medicine
Kazutoshi Shibuya: Toho University School of Medicine
Tetuo Mikami: Toho University School of Medicine
Naohiro Inohara: University of Michigan Medical School
Kouji Matsushima: Tokyo University of Science
Norihiro Tada: Juntendo University School of Medicine
Hiroyasu Nakano: Toho University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-20

Abstract: Abstract Interleukin (IL)-11 is a member of the IL-6 family of cytokines and is 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 generate Il11 reporter mice. IL-11+ cells appear in the colon in murine tumor and acute colitis models. Il11ra1 or Il11 deletion attenuates the development of colitis-associated colorectal cancer. IL-11+ cells express fibroblast markers and genes associated with cell proliferation and tissue repair. IL-11 induces the activation of colonic fibroblasts and epithelial cells through phosphorylation of STAT3. Human cancer database analysis reveals that the expression of genes enriched in IL-11+ fibroblasts is elevated in human colorectal cancer and correlated with reduced recurrence-free survival. IL-11+ fibroblasts activate both tumor cells and fibroblasts via secretion of IL-11, thereby constituting a feed-forward loop between tumor cells and fibroblasts in the tumor microenvironment.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22450-3

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DOI: 10.1038/s41467-021-22450-3

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