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

Author

Listed:
  • 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
    Tokyo University of Science)

  • Masato Ohtsuka

    (Tokai University
    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
    Toho University School of Medicine)

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.

Suggested Citation

  • Takashi Nishina & Yutaka Deguchi & Daisuke Ohshima & Wakami Takeda & Masato Ohtsuka & Shigeyuki Shichino & Satoshi Ueha & Soh Yamazaki & Mika Kawauchi & Eri Nakamura & Chiharu Nishiyama & Yuko Kojima , 2021. "Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22450-3
    DOI: 10.1038/s41467-021-22450-3
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