ArticlePloS one2015
Tracheal dysplasia precedes bronchial dysplasia in mouse model of N-nitroso trischloroethylurea induced squamous cell lung cancer.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 22 citations in OpenAlex.
- Rho-associated kinase (ROCK)-associated proteins and genes-encoded proteins upregulated in lung squamous cell carcinoma (LUSC).Journal of the Egyptian National Cancer Institute · 2026Article
- Aberrant basal cell clonal dynamics shape early lung carcinogenesis.Science (New York, N.Y.) · 2025Article
- Premalignant Progression in the Lung: Knowledge Gaps and Novel Opportunities for Interception of Non-Small Cell Lung Cancer. An Official American Thoracic Society Research Statement.American journal of respiratory and critical care medicine · 2024Review
- Aucubin Alleviates Chronic Obstructive Pulmonary Disease by Activating Nrf2/HO-1 Signaling Pathway.Cell biochemistry and biophysics · 2024Article
- Article
- Hydrogel-Embedded Precision-Cut Lung Slices Model Lung Cancer Premalignancy Ex Vivo.Advanced healthcare materials · 2024Article
- Lipid-Sensing Receptor FFAR4 Modulates Pulmonary Epithelial Homeostasis following Immunogenic Exposures Independently of the FFAR4 Ligand Docosahexaenoic Acid (DHA).International journal of molecular sciences · 2023Article
- Pre-clinical lung squamous cell carcinoma mouse models to identify novel biomarkers and therapeutic interventions.Frontiers in oncology · 2023Review
- NTCU induced pre-malignant and malignant stages of lung squamous cell carcinoma in mice model.Scientific reports · 2021Article
- Mapping lung squamous cell carcinoma pathogenesis through in vitro and in vivo models.Communications biology · 2021Review
- An Improved Murine Premalignant Squamous Cell Model: Tobacco Smoke Exposure Augments NTCU-Induced Murine Airway Dysplasia.Cancer prevention research (Philadelphia, Pa.) · 2021Article
- Two-stage 3-methylcholanthrene and butylated hydroxytoluene-induced lung carcinogenesis in mice.Methods in cell biology · 2021Article
- Progress towards non-small-cell lung cancer models that represent clinical evolutionary trajectories.Open biology · 2021Review
- Toll-like receptor 4-mediated respiratory syncytial virus disease and lung transcriptomics in differentially susceptible inbred mouse strains.Physiological genomics · 2019Article
- The Effect of Mouse Strain, Sex, and Carcinogen Dose on Toxicity and the Development of Lung Dysplasia and Squamous Cell Carcinomas in Mice.Cancer prevention research (Philadelphia, Pa.) · 2019Article
- Airway brushing as a new experimental methodology to detect airway gene expression signatures in mouse lung squamous cell carcinoma.Scientific reports · 2018Article
- Proceedings: Regenerative Medicine for Lung Diseases: A CIRM Workshop Report.Stem cells translational medicine · 2017Article
- Understanding the Relevance of the Mouse Cigarette Smoke Model of COPD: Peering through the Smoke.American journal of respiratory cell and molecular biology · 2017Article
- microRNA-802/Rnd3 pathway imposes on carcinogenesis and metastasis of fine particulate matter exposure.Oncotarget · 2016Article
- Role of deltaNp63(pos)CD44v(pos) cells in the development of N-nitroso-tris-chloroethylurea-induced peripheral-type mouse lung squamous cell carcinomas.Cancer science · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Squamous cell lung cancer (SCC) is the second leading cause of lung cancer death in the US and has a 5-year survival rate of only 16%. Histological changes in the bronchial epithelium termed dysplasia are precursors to invasive SCC. However, the cellular mechanisms that cause dysplasia are unknown. To fill this knowledge gap, we used topical application of N-nitroso-tris chloroethylurea (NTCU) for 32 weeks to induce squamous dysplasia and SCC in mice. At 32 weeks the predominant cell type in the dysplastic airways was Keratin (K) 5 and K14 expressing basal cells. Notably, basal cells are extremely rare in the normal mouse bronchial epithelium but are abundant in the trachea. We therefore evaluated time-dependent changes in tracheal and bronchial histopathology after NTCU exposure (4, 8, 12, 16, 25 and 32 weeks). We show that tracheal dysplasia occurs significantly earlier than that of the bronchial epithelium (12 weeks vs. 25 weeks). This was associated with increased numbers of K5+/K14+ tracheal basal cells and a complete loss of secretory (Club cell secretory protein expressing CCSP+) and ciliated cells. TUNEL staining of NTCU treated tissues confirmed that the loss of CCSP+ and ciliated cells was not due to apoptosis. However, mitotic index (measured by bromodeoxyuridine incorporation) showed that NTCU treatment increased proliferation of K5+ basal cells in the trachea, and altered bronchial mitotic population from CCSP+ to K5+ basal cells. Thus, we demonstrate that NTCU-induced lung epithelial dysplasia starts in the tracheal epithelium, and is followed by basal cell metaplasia of the bronchial epithelium. This analysis extends our knowledge of the NTCU-SCC model by defining the early changes in epithelial cell phenotypes in distinct airway locations, and this may assist in identifying new targets for future chemoprevention studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.