TY - JOUR T1 - Interleukin-11 is a Marker for Both Cancer- and Inflammation-Associated Fibroblasts that Contribute to Colorectal Cancer Progression JF - bioRxiv DO - 10.1101/2020.01.25.919795 SP - 2020.01.25.919795 AU - Takashi Nishina AU - Yutaka Deguchi AU - Wakami Takeda AU - Masato Ohtsuka AU - Daisuke Ohshima AU - Soh Yamazaki AU - Mika Kawauchi AU - Eri Nakamura AU - Chiharu Nishiyama AU - Yuko Kojima AU - Satomi Adachi-Akahane AU - Mizuho Hasegawa AU - Mizuho Nakayama AU - Masanobu Oshima AU - Hideo Yagita AU - Kazutoshi Shibuya AU - Tetuo Mikami AU - Naohiro Inohara AU - Norihiro Tada AU - Hiroyasu Nakano Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/01/26/2020.01.25.919795.abstract N2 - 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. ER -