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

Nishina, T.; Deguchi, Y.; Takeda, W.; Ohtsuka, M.; Ohshima, D.; Yamazaki, S.; Kawauchi, M.; Nakamura, E.; Nishiyama, C.; Kojima, Y.; Adachi-Akemi, S.; Hasegawa, M.; Nakayama, M.; Ohshima, M.; Yagita, H.; Shibuya, K.; Mikami, T.; Inohara, N.; Tada, N.; Nakano, H.

doi:10.1101/2020.01.25.919795

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bioRxiv · 10.1101/2020.01.25.919795

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

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Abstract

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.

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Nishina, T., Deguchi, Y., Takeda, W., Ohtsuka, M., Ohshima, D., Yamazaki, S., Kawauchi, M., Nakamura, E., Nishiyama, C., Kojima, Y., Adachi-Akemi, S., Hasegawa, M., Nakayama, M., Ohshima, M., Yagita, H., Shibuya, K., Mikami, T., Inohara, N., Tada, N., Nakano, H.. 2020-01-26. Interleukin-11 is a Marker for Both Cancer- and Inflammation-Associated Fibroblasts that Contribute to Colorectal Cancer Progression. https://doi.org/10.1101/2020.01.25.919795

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