IL-1β transgenic mouse model of inflammation driven esophageal and oral squamous cell carcinoma.
IL-1β transgenic mouse model of inflammation driven esophageal and oral squamous cell carcinoma.
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DOI：
10.1038/s41598-023-39907-8
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发表时间：
2023-08-05
影响因子：
4.6
通讯作者：
Fox, James G.
中科院分区：
文献类型：
--
作者：
Muthupalani, Sureshkumar;Annamalai, Damodaran;Feng, Yan;Ganesan, Suresh M.;Ge, Zhongming;Whary, Mark T.;Nakagawa, Hiroshi;Rustgi, Anil K.;Wang, Timothy C.;Fox, James G.
慢性炎症是食管腺癌（EAC）和食管鳞状细胞癌（ESCC）发展的组成部分，尽管后者与反流性食管炎无关。在口腔、食管和前胃鳞状上皮中表达人白细胞介素（IL）-1β的L2-IL-1β转基因小鼠的特征是慢性炎症和鳞状-柱状连接处Barrett食管样化生、异型增生和腺癌的逐步发展。然而，IL-1β介导的慢性炎症在口腔和食管鳞状上皮中的功能后果仍然难以捉摸。我们首次报告，除了先前描述的Barrett食管样化生外，L2-IL-1β小鼠还发生鳞状上皮异型增生，并进展为食管和舌鳞状细胞癌（SCC）。L2-IL-1β显示鳞状不典型增生向SCC的年龄依赖性进展，在12-15月龄时，食管和舌浸润性SCC的发生率分别约为40%（n = 49）和23.5%（n = 17）。有趣的是，L2-IL-1β中的SCC发展和进展在无菌（GF）和无特异性病原体（SPF）条件下相似。免疫组织化学显示，在L2-IL-1β小鼠的异型增生鳞状上皮中，T细胞占主导地位的炎症特征，Ki 67、Sox 2和DNA双链断裂标记物γ-H2 AX的表达增强。在L2-IL-1β小鼠的食管和舌组织中，促炎细胞因子、免疫调节因子、炎性细胞（T细胞、中性粒细胞、嗜酸性粒细胞和巨噬细胞）的化学引诱物和氧化损伤标志物iNOS显著增加。我们最近的研究结果扩展了IL-1β小鼠模型的转化效用，以帮助进一步表征炎症驱动的BE和EAC以及ESCC和口腔SCC的关键途径。
Chronic inflammation is integral to the development of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), although the latter has not been associated with reflux esophagitis. The L2-IL-1β transgenic mice, expressing human interleukin (IL)-1β in the oral, esophageal and forestomach squamous epithelia feature chronic inflammation and a stepwise development of Barrett’s esophagus-like metaplasia, dysplasia and adenocarcinoma at the squamo-columnar junction. However, the functional consequences of IL-1β-mediated chronic inflammation in the oral and esophageal squamous epithelia remain elusive. We report for the first time that in addition to the previously described Barrett’s esophagus-like metaplasia, the L2-IL-1β mice also develop squamous epithelial dysplasia with progression to squamous cell carcinoma (SCC) in the esophagus and the tongue. L2-IL-1β showed age-dependent progression of squamous dysplasia to SCC with approximately 40% (n = 49) and 23.5% (n = 17) incidence rates for esophageal and tongue invasive SCC respectively, by 12–15 months of age. Interestingly, SCC development and progression in L2-IL-1β was similar in both Germ Free (GF) and Specific Pathogen Free (SPF) conditions. Immunohistochemistry revealed a T cell predominant inflammatory profile with enhanced expression of Ki67, Sox2 and the DNA double-strand break marker, γ-H2AX, in the dysplastic squamous epithelia of L2-IL-1β mice. Pro-inflammatory cytokines, immunomodulatory players, chemoattractants for inflammatory cells (T cells, neutrophils, eosinophils, and macrophages) and oxidative damage marker, iNOS, were significantly increased in the esophageal and tongue tissues of L2-IL-1β mice. Our recent findings have expanded the translational utility of the IL-1β mouse model to aid in further characterization of the key pathways of inflammation driven BE and EAC as well as ESCC and Oral SCC.
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DOI：
10.1158/1078-0432.ccr-15-1761
发表时间：
2016-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Gleber-Netto FO;Yakob M;Li F;Feng Z;Dai J;Kao HK;Chang YL;Chang KP;Wong DT
通讯作者：
Wong DT
Interleukin-1家族：回到未来。
影响因子：
32.4
作者：
Garlanda C;Dinarello CA;Mantovani A
通讯作者：
Mantovani A
影响因子：
5.8
作者：
Cui, Guanglin;Ren, Jingli;Yuan, Aping
通讯作者：
Yuan, Aping
影响因子：
--
作者：
Lin R;Zhang C;Zheng J;Tian D;Lei Z;Chen D;Xu Z;Su M
通讯作者：
Su M
影响因子：
11.1
作者：
Chen, Lih-Chyang;Wang, Li-Jie;Tsang, Nang-Ming;Ojcius, David M.;Chen, Chia-Chun;OuYang, Chun-Nan;Hsueh, Chuen;Liang, Ying;Chang, Kai-Ping;Chen, Chiu-Chin;Chang, Yu-Sun
通讯作者：
Chang, Yu-Sun