Advanced

Club cells form lung adenocarcinomas and maintain the alveoli of adult mice

Spella, Magda; Lilis, Ioannis; Pepe, Mario Aa; Chen, Yuanyuan; Armaka, Maria; Lamort, Anne-Sophie; Zazara, Dimitra E; Roumelioti, Fani; Vreka, Malamati and Kanellakis, Nikolaos I, et al. (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)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
publishing date
type
Contribution to journal
publication status
published
subject
in
eLife
volume
8
publisher
eLife Sciences Publications LTD.
external identifiers
  • scopus:85069265418
ISSN
2050-084X
DOI
10.7554/eLife.45571
language
English
LU publication?
no
id
f6f511aa-cd34-4047-b682-0fbfad430833
date added to LUP
2019-06-02 09:18:26
date last changed
2019-09-15 05:18:43
@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 LTD.},
  series       = {eLife},
  title        = {Club cells form lung adenocarcinomas and maintain the alveoli of adult mice},
  url          = {http://dx.doi.org/10.7554/eLife.45571},
  volume       = {8},
  year         = {2019},
}