Interleukin-11 is a Marker for Both Cancer- and Inflammation-Associated Fibroblasts that Contribute to Colorectal Cancer Progression
Takashi Nishina, et al.
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-11+ fibroblasts, and that a feed-forward loop between IL-11 and IL-11+ fibroblasts might contribute to tumor development.
Read in full at bioRxiv.
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 It has not been peer reviewed but is currently under consideration at Nature Communications.