Interleukin-11 is a Marker for Both Cancer- and Inflammation-Associated Fibroblasts that Contribute to Colorectal Cancer Progression
Interleukin-11 is a Marker for Both Cancer- and Inflammation-Associated Fibroblasts that Contribute to Colorectal Cancer Progression
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DOI：
10.1101/2020.01.25.919795
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发表时间：
2020-01
期刊：
影响因子：
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通讯作者：
T. Nishina;Y. Deguchi;Wakami Takeda;M. Ohtsuka;Daisuke Ohshima;S. Yamazaki;Mika Kawauchi;Eri Nakamura
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文献类型：
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作者：
T. Nishina;Y. Deguchi;Wakami Takeda;M. Ohtsuka;Daisuke Ohshima;S. Yamazaki;Mika Kawauchi;Eri Nakamura
白细胞介素（IL）-11是细胞因子IL-6家族的成员，并且参与多种细胞应答，包括肿瘤发展。然而，IL-11产生细胞（IL-11+）的起源和功能尚未完全了解。为了在体内表征IL-11+细胞，我们产生了IL 11报告小鼠。IL-11+细胞出现在三种鼠肿瘤模型和一种鼠急性结肠炎模型的结肠中。Il 11 ra 1或Il 11缺失可减弱结肠炎相关结直肠癌的发展。IL-11+细胞表达成纤维细胞标志物以及与细胞增殖和组织修复相关的基因。IL-11诱导结肠成纤维细胞中的STAT 3磷酸化，表明IL-11+成纤维细胞的活化。使用人类癌症数据库进行的分析显示，IL-11+成纤维细胞中富集的基因在人类结直肠癌中升高，并与无病生存率降低相关。总之，我们的结果表明，肿瘤细胞诱导IL-11+成纤维细胞，IL-11和IL-11+成纤维细胞之间的前馈回路可能有助于肿瘤的发展。
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.