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- Title
Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer.
- Authors
Nishina, Takashi; Deguchi, Yutaka; Ohshima, Daisuke; Takeda, Wakami; Ohtsuka, Masato; Shichino, Shigeyuki; Ueha, Satoshi; Yamazaki, Soh; Kawauchi, Mika; Nakamura, Eri; Nishiyama, Chiharu; Kojima, Yuko; Adachi-Akahane, Satomi; Hasegawa, Mizuho; Nakayama, Mizuho; Oshima, Masanobu; Yagita, Hideo; Shibuya, Kazutoshi; Mikami, Tetuo; Inohara, Naohiro
- 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. The stromal fibroblast population in the colon is composed of heterogeneous and distinct cell subtypes that play a crucial role in the development of colitis and colon cancer. Here the authors generate IL-11 reporter mice and characterize the origin and phenotype of inflammatory IL-11+ fibroblasts in colitis and colon cancer preclinical models.
- Subjects
COLORECTAL cancer; GENES; FIBROBLASTS; COLON cancer; INFLAMMATORY bowel diseases; INTERLEUKIN-27
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-22450-3