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表达白细胞介素-11 的成纤维细胞具有独特的基因特征，与结直肠癌的不良预后相关。

Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer.

机构信息

Department of Biochemistry, Toho University School of Medicine, Tokyo, Japan.

Department of Physiology, Toho University School of Medicine, Tokyo, Japan.

出版信息

Nat Commun. 2021 Apr 16;12(1):2281. doi: 10.1038/s41467-021-22450-3.

DOI:10.1038/s41467-021-22450-3
PMID:33863879
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8052408/
Abstract

Interleukin (IL)-11 is a member of the IL-6 family of cytokines and is 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 generate Il11 reporter mice. IL-11 cells appear in the colon in murine tumor and acute colitis models. Il11ra1 or Il11 deletion attenuates the development of colitis-associated colorectal cancer. IL-11 cells express fibroblast markers and genes associated with cell proliferation and tissue repair. IL-11 induces the activation of colonic fibroblasts and epithelial cells through phosphorylation of STAT3. Human cancer database analysis reveals that the expression of genes enriched in IL-11 fibroblasts is elevated in human colorectal cancer and correlated with reduced recurrence-free survival. IL-11 fibroblasts activate both tumor cells and fibroblasts via secretion of IL-11, thereby constituting a feed-forward loop between tumor cells and fibroblasts in the tumor microenvironment.

摘要

白细胞介素 (IL)-11 是细胞因子 IL-6 家族的成员，参与多种细胞反应，包括肿瘤的发展。然而，IL-11 产生细胞 (IL-11 细胞) 的起源和功能尚未完全阐明。为了在体内表征 IL-11 细胞，我们生成了 Il11 报告小鼠。在小鼠肿瘤和急性结肠炎模型中，IL-11 细胞出现在结肠中。Il11ra1 或 Il11 缺失可减轻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和与细胞增殖和组织修复相关的基因。IL-11 通过 STAT3 的磷酸化诱导结肠成纤维细胞和上皮细胞的激活。人类癌症数据库分析显示，在人类结直肠癌中，富含 IL-11 成纤维细胞的基因表达上调，并与无复发生存率降低相关。IL-11 成纤维细胞通过分泌 IL-11 激活肿瘤细胞和成纤维细胞，从而在肿瘤微环境中构成肿瘤细胞和成纤维细胞之间的正反馈回路。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e55/8052408/37bc68c4c030/41467_2021_22450_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e55/8052408/05aed9297229/41467_2021_22450_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e55/8052408/b3af37926ff6/41467_2021_22450_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e55/8052408/9d906e88b66f/41467_2021_22450_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e55/8052408/95304f1f829f/41467_2021_22450_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e55/8052408/be30daf04972/41467_2021_22450_Fig9_HTML.jpg
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