Chitinase 3-Like-1 Expression in Colonic Epithelial Cells as a Potentially Novel Marker for Colitis-Associated Neoplasia
Chitinase 3-Like-1 Expression in Colonic Epithelial Cells as a Potentially Novel Marker for Colitis-Associated Neoplasia
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DOI：
10.1016/j.ajpath.2011.05.038
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发表时间：
2011-09-01
影响因子：
6
通讯作者：
Mizoguchi, Emiko
中科院分区：
文献类型：
--
作者：
Chen, Chun-Chuan;Pekow, Joel;Mizoguchi, Emiko
几丁质酶3-样-1(CHI3L1/YKL-40)是一种由结肠上皮细胞(CECs)和巨噬细胞等限制性细胞分泌的蛋白质。CHI3L1是一种炎症相关分子，在结肠炎和结肠癌患者中表达增强。CHI3L1对CECs的生物学功能尚不清楚。在这项研究中，我们研究了CHI3L1在结肠炎相关肿瘤发生发展过程中对CECs的作用。我们分析了来自健康人和有或无癌前病变或恶变的溃疡性结肠炎患者的结肠样本。DNA芯片和RT-PCR分析显示，炎症性肠病(IBD)伴异型增生/腺癌患者非异型增生黏膜中CHI3L1的表达显著高于正常对照组和无异型增生的IBD患者。经MC检测，CHI3L1在溃疡性结肠炎伴远端不典型增生患者的结肠活检组织中表达于特定细胞类型。纯化的CHI3L1有效激活了人结肠癌SW480细胞的核因子-kappaB信号通路，促进了IL-8和TNF-α的分泌。此外，CHI3L1对结肠癌细胞的增殖和迁移有明显的促进作用。综上所述，CHI3L1可能参与炎症条件下CECs的增殖、迁移和肿瘤进展，并可能成为IBD患者肿瘤变化的有用生物标志物。(Am J Pathol2011,179：14941503；doi：10.1016/j.ajpath.2011.05.038)
Chitinase 3-like-1 (CHI3L1/YKL-40) is a protein secreted from restricted cell types including colonic epithelial cells (CECs) and macrophages. CHI3L1 is an inflammation-associated molecule, and its expression is enhanced in persons with colitis and colon cancer. The biological function of CHI3L1 on CECs is unclear. In this study, we investigated the role of CHI3L1 on CECs during the development of colitis-associated neoplasia. We analyzed colonic samples obtained from healthy persons and from persons with ulcerative colitis with or without premalignant or malignant changes. DNA microarray and RT-PCR analyses significantly increased CHI3L1 expression in non-dysplastic mucosa from patients with inflammatory bowel disease (IBD) who had dysplasia/adenocarcinoma compared with that in healthy persons and in patients with IBD who did not have dysplasia. As determined by MC, CHI3L1 was expressed in specific cell types in the crypts of colonic biopsies obtained from patients with ulcerative colitis who have remote dysplasia. Purified CHI3L1 efficiently activated the NF-kappa B signaling pathway and enhanced the secretion of IL-8 and TNF-alpha in SW480 human colon cancer cells. In addition, colon cancer cell proliferation and migration were significantly promoted in response to CHI3L1 in these cells. In summary, CHI3L1 may contribute to the proliferation, migration, and neoplastic progression of CECs under inflammatory conditions and could be a useful biomarker for neoplastic changes in patients with IBD. (Am J Pathol 2011, 179:1494-1503; DOI: 10.1016/j.ajpath.2011.05.038)