PT  - JOURNAL ARTICLE
AU  - Behrend, Sabine J.
AU  - Giotopoulou, Georgia A.
AU  - Spella, Magda
AU  - Stathopoulos, Georgios T.
TI  - A role for club cells in smoking-associated lung adenocarcinoma
AID  - 10.1183/16000617.0122-2021
DP  - 2021 Dec 31
TA  - European Respiratory Review
PG  - 210122
VI  - 30
IP  - 162
4099  - http://err.ersjournals.com/content/30/162/210122.short
4100  - http://err.ersjournals.com/content/30/162/210122.full
SO  - EUROPEAN RESPIRATORY REVIEW2021 Dec 31; 30
AB  - The cellular origin of lung adenocarcinoma remains a focus of intense research efforts. The marked cellular heterogeneity and plasticity of the lungs, as well as the vast variety of molecular subtypes of lung adenocarcinomas perplex the field and account for the extensive variability of experimental results. While most experts would agree on the cellular origins of other types of thoracic tumours, great controversy exists on the tumour-initiating cells of lung adenocarcinoma, since this histologic subtype of lung cancer arises in the distal pulmonary regions where airways and alveoli converge, occurs in smokers as well as nonsmokers, is likely caused by various environmental agents, and is marked by vast molecular and pathologic heterogeneity. Alveolar type II, club, and their variant cells have all been implicated in lung adenocarcinoma progeny and the lineage hierarchies in the distal lung remain disputed. Here we review the relevant literature in this rapidly expanding field, including results from mouse models and human studies. In addition, we present a case for club cells as cells of origin of lung adenocarcinomas that arise in smokers.Multiple lung epithelial cells are targets of carcinogenic hits. Club cells are such cells that can metabolically activate tobacco pre-carcinogens, being thus positioned as cells of origin of lung adenocarcinomas in smokers. https://bit.ly/3iOshcy