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

Takashi Nishina, et al.

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Received Date: 10th January 20

Takashi Nishina, Yutaka Deguchi, Wakami Takeda,  Masato Ohtsuka,  Daisuke Ohshima, Soh Yamazaki, Mika Kawauchi, Eri Nakamura,  Chiharu Nishiyama,  Yuko Kojima,  Satomi Adachi-Akemi, Mizuho Hasegawa, Mizuho Nakayama, Masanobu Ohshima,  Hideo Yagita, Kazutoshi Shibuya,  Tetuo Mikami,  Naohiro Inohara,  Norihiro Tada,  Hiroyasu Nakano

Interleukin (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-11fibroblasts, and that a feed-forward loop between IL-11 and IL-11+ fibroblasts might contribute to tumor development.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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