1. Academic Validation
  2. Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer

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

  • Nat Commun. 2021 Apr 16;12(1):2281. doi: 10.1038/s41467-021-22450-3.
Takashi Nishina 1 Yutaka Deguchi 2 Daisuke Ohshima 3 Wakami Takeda 2 4 Masato Ohtsuka 5 6 Shigeyuki Shichino 7 Satoshi Ueha 7 Soh Yamazaki 2 Mika Kawauchi 2 Eri Nakamura 8 Chiharu Nishiyama 4 Yuko Kojima 9 Satomi Adachi-Akahane 3 Mizuho Hasegawa 10 Mizuho Nakayama 11 Masanobu Oshima 11 Hideo Yagita 12 Kazutoshi Shibuya 13 Tetuo Mikami 14 Naohiro Inohara 10 Kouji Matsushima 7 Norihiro Tada 8 Hiroyasu Nakano 15 16
Affiliations

Affiliations

  • 1 Department of Biochemistry, Toho University School of Medicine, Tokyo, Japan. takashi.nishina@med.toho-u.ac.jp.
  • 2 Department of Biochemistry, Toho University School of Medicine, Tokyo, Japan.
  • 3 Department of Physiology, Toho University School of Medicine, Tokyo, Japan.
  • 4 Laboratory of Molecular Biology and Immunology, Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo, Japan.
  • 5 Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, School of Medicine, Tokai University, Isehara, Kanagawa, Japan.
  • 6 The Institute of Medical Sciences, Tokai University, Isehara, Kanagawa, Japan.
  • 7 Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan.
  • 8 Research Institute for Diseases of Old Age, Juntendo University School of Medicine, Tokyo, Japan.
  • 9 Laboratory of Morphology and Image Analysis, Research Support Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • 10 Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
  • 11 WPI Nano Life Science Institute (WPI-Nano LSI), Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan.
  • 12 Department of Immunology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • 13 Department of Surgical Pathology, Toho University School of Medicine, Tokyo, Japan.
  • 14 Department of Pathology, Toho University School of Medicine, Tokyo, Japan.
  • 15 Department of Biochemistry, Toho University School of Medicine, Tokyo, Japan. hiroyasu.nakano@med.toho-u.ac.jp.
  • 16 Host Defense Research Center, Toho University School of Medicine, Tokyo, Japan. hiroyasu.nakano@med.toho-u.ac.jp.
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.

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