Club cells form lung adenocarcinomas and maintain the alveoli of adult mice
(2019) In eLife 8.- Abstract
Lung cancer and chronic lung diseases impose major disease burdens worldwide and are caused by inhaled noxious agents including tobacco smoke. The cellular origins of environmental-induced lung tumors and of the dysfunctional airway and alveolar epithelial turnover observed with chronic lung diseases are unknown. To address this, we combined mouse models of genetic labeling and ablation of airway (club) and alveolar cells with exposure to environmental noxious and carcinogenic agents. Club cells are shown to survive KRAS mutations and to form lung tumors after tobacco carcinogen exposure. Increasing numbers of club cells are found in the alveoli with aging and after lung injury, but go undetected since they express alveolar proteins.... (More)
Lung cancer and chronic lung diseases impose major disease burdens worldwide and are caused by inhaled noxious agents including tobacco smoke. The cellular origins of environmental-induced lung tumors and of the dysfunctional airway and alveolar epithelial turnover observed with chronic lung diseases are unknown. To address this, we combined mouse models of genetic labeling and ablation of airway (club) and alveolar cells with exposure to environmental noxious and carcinogenic agents. Club cells are shown to survive KRAS mutations and to form lung tumors after tobacco carcinogen exposure. Increasing numbers of club cells are found in the alveoli with aging and after lung injury, but go undetected since they express alveolar proteins. Ablation of club cells prevents chemical lung tumors and causes alveolar destruction in adult mice. Hence club cells are important in alveolar maintenance and carcinogenesis and may be a therapeutic target against premalignancy and chronic lung disease.
(Less)
- author
- publishing date
- 2019-05-29
- type
- Contribution to journal
- publication status
- published
- subject
- in
- eLife
- volume
- 8
- publisher
- eLife Sciences Publications
- external identifiers
-
- pmid:31140976
- scopus:85069265418
- ISSN
- 2050-084X
- DOI
- 10.7554/eLife.45571
- language
- English
- LU publication?
- no
- additional info
- © 2019, Spella et al.
- id
- f6f511aa-cd34-4047-b682-0fbfad430833
- date added to LUP
- 2019-06-02 09:18:26
- date last changed
- 2024-04-16 09:59:29
@article{f6f511aa-cd34-4047-b682-0fbfad430833, abstract = {{<p>Lung cancer and chronic lung diseases impose major disease burdens worldwide and are caused by inhaled noxious agents including tobacco smoke. The cellular origins of environmental-induced lung tumors and of the dysfunctional airway and alveolar epithelial turnover observed with chronic lung diseases are unknown. To address this, we combined mouse models of genetic labeling and ablation of airway (club) and alveolar cells with exposure to environmental noxious and carcinogenic agents. Club cells are shown to survive KRAS mutations and to form lung tumors after tobacco carcinogen exposure. Increasing numbers of club cells are found in the alveoli with aging and after lung injury, but go undetected since they express alveolar proteins. Ablation of club cells prevents chemical lung tumors and causes alveolar destruction in adult mice. Hence club cells are important in alveolar maintenance and carcinogenesis and may be a therapeutic target against premalignancy and chronic lung disease.</p>}}, author = {{Spella, Magda and Lilis, Ioannis and Pepe, Mario Aa and Chen, Yuanyuan and Armaka, Maria and Lamort, Anne-Sophie and Zazara, Dimitra E and Roumelioti, Fani and Vreka, Malamati and Kanellakis, Nikolaos I and Wagner, Darcy E and Giannou, Anastasios D and Armenis, Vasileios and Arendt, Kristina Am and Klotz, Laura V and Toumpanakis, Dimitrios and Karavana, Vassiliki and Zakynthinos, Spyros G and Giopanou, Ioanna and Marazioti, Antonia and Aidinis, Vassilis and Sotillo, Rocio and Stathopoulos, Georgios T}}, issn = {{2050-084X}}, language = {{eng}}, month = {{05}}, publisher = {{eLife Sciences Publications}}, series = {{eLife}}, title = {{Club cells form lung adenocarcinomas and maintain the alveoli of adult mice}}, url = {{http://dx.doi.org/10.7554/eLife.45571}}, doi = {{10.7554/eLife.45571}}, volume = {{8}}, year = {{2019}}, }