An Improved Murine Premalignant Squamous Cell Model: Tobacco Smoke Exposure Augments NTCU-Induced Murine Airway Dysplasia.
An Improved Murine Premalignant Squamous Cell Model: Tobacco Smoke Exposure Augments NTCU-Induced Murine Airway Dysplasia.
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一种改进的小鼠癌前鳞状细胞模型：烟草烟雾暴露增强NTCU诱导的小鼠气道发育不良。
DOI：
10.1158/1940-6207.capr-20-0332
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Keith RL
中科院分区：
文献类型：
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作者：
Dwyer-Nield LD;McArthur DG;Tennis MA;Merrick DT;Keith RL
烟草烟雾诱发的鳞状细胞肺癌从支气管内发育不良病变发展为侵袭性疾病。一种重现在当前和既往吸烟者中观察到的组织学进展的可重复小鼠模型将推进新的预防和治疗策略的测试。先前的研究表明，长期局部应用N-亚硝基-三-氯乙基脲（NTCU）在敏感小鼠中产生一系列气道病变，类似于人类慢性烟草烟雾暴露引起的气道病变。为了改进目前的NTCU模型并使其更好地与人类疾病相一致，将NTCU每周两次应用于小鼠，持续4-5周，然后是恢复期，然后再暴露于香烟烟雾（CS）或环境空气（对照）3-6周。尽管时间进程短，但与对照小鼠相比，CS的添加导致显著更多的癌前病变（PML）（2.6 vs 0.5; p<0.02），并导致更少的肺泡巨噬细胞（52，000个巨噬细胞/ml BALF vs 68，000; p<0.05）。这种改进的NTCU + CS模型是第一个纳入烟草烟雾的鼠鳞状细胞肺癌模型，并且更适合临床前研究，因为PML数量增加，所需小鼠数量减少，PML发展所需时间减少。
Tobacco smoke-induced squamous cell lung cancer develops from endobronchial dysplastic lesions that progress to invasive disease. A reproducible murine model recapitulating histologic progression observed in current and former smokers will advance testing of new preventive and therapeutic strategies. Previous studies show that prolonged topical application of N-nitroso-tris-chloroethylurea (NTCU) generates a range of airway lesions in sensitive mice similar to those induced by chronic tobacco smoke exposure in humans. To improve the current NTCU model and better align it with human disease, NTCU was applied to mice twice weekly for 4–5 weeks followed by a recovery period before cigarette smoke (CS) or ambient air (control) exposure for an additional 3–6 weeks. Despite the short time course, the addition of CS led to significantly more premalignant lesions (PML) (2.6 vs 0.5; p<0.02) and resulted in fewer alveolar macrophages (52,000 macrophages/ml BALF vs 68,000; p<0.05) compared to control mice. This improved NTCU + CS model is the first murine squamous cell lung cancer model to incorporate tobacco smoke and is more amenable to pre-clinical studies because of the increased number of PML, decreased number of mice required, and reduced time needed for PML development.