eLife (May 2019)
Club cells form lung adenocarcinomas and maintain the alveoli of adult mice
- Magda Spella,
- Ioannis Lilis,
- Mario AA Pepe,
- Yuanyuan Chen,
- Maria Armaka,
- Anne-Sophie Lamort,
- Dimitra E Zazara,
- Fani Roumelioti,
- Malamati Vreka,
- Nikolaos I Kanellakis,
- Darcy E Wagner,
- Anastasios D Giannou,
- Vasileios Armenis,
- Kristina AM Arendt,
- Laura V Klotz,
- Dimitrios Toumpanakis,
- Vassiliki Karavana,
- Spyros G Zakynthinos,
- Ioanna Giopanou,
- Antonia Marazioti,
- Vassilis Aidinis,
- Rocio Sotillo,
- Georgios T Stathopoulos
Affiliations
- Magda Spella
- ORCiD
- Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio, Greece
- Ioannis Lilis
- Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio, Greece
- Mario AA Pepe
- Comprehensive Pneumology Center (CPC), Institute for Lung Biology and Disease (iLBD), University Hospital, Ludwig-Maximilians University, Helmholtz Center Munich, The German Center for Lung Research (DZL), Munich, Germany
- Yuanyuan Chen
- Division of Molecular Thoracic Oncology, Translational Lung Research Center (TLRC), German Cancer Research Center (DKFZ), The German Center for Lung Research (DZL), Heidelberg, Germany
- Maria Armaka
- Institute of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Vari, Greece
- Anne-Sophie Lamort
- Comprehensive Pneumology Center (CPC), Institute for Lung Biology and Disease (iLBD), University Hospital, Ludwig-Maximilians University, Helmholtz Center Munich, The German Center for Lung Research (DZL), Munich, Germany
- Dimitra E Zazara
- Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio, Greece
- Fani Roumelioti
- Institute of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Vari, Greece
- Malamati Vreka
- Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio, Greece; Comprehensive Pneumology Center (CPC), Institute for Lung Biology and Disease (iLBD), University Hospital, Ludwig-Maximilians University, Helmholtz Center Munich, The German Center for Lung Research (DZL), Munich, Germany
- Nikolaos I Kanellakis
- Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio, Greece
- Darcy E Wagner
- Comprehensive Pneumology Center (CPC), Institute for Lung Biology and Disease (iLBD), University Hospital, Ludwig-Maximilians University, Helmholtz Center Munich, The German Center for Lung Research (DZL), Munich, Germany
- Anastasios D Giannou
- Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio, Greece
- Vasileios Armenis
- Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio, Greece
- Kristina AM Arendt
- Comprehensive Pneumology Center (CPC), Institute for Lung Biology and Disease (iLBD), University Hospital, Ludwig-Maximilians University, Helmholtz Center Munich, The German Center for Lung Research (DZL), Munich, Germany
- Laura V Klotz
- Comprehensive Pneumology Center (CPC), Institute for Lung Biology and Disease (iLBD), University Hospital, Ludwig-Maximilians University, Helmholtz Center Munich, The German Center for Lung Research (DZL), Munich, Germany
- Dimitrios Toumpanakis
- First Department of Critical Care Medicine and Pulmonary Services, School of Medicine, Evangelismos Hospital, National and Kapodistrian University of Athens, Athens, Greece
- Vassiliki Karavana
- First Department of Critical Care Medicine and Pulmonary Services, School of Medicine, Evangelismos Hospital, National and Kapodistrian University of Athens, Athens, Greece
- Spyros G Zakynthinos
- First Department of Critical Care Medicine and Pulmonary Services, School of Medicine, Evangelismos Hospital, National and Kapodistrian University of Athens, Athens, Greece
- Ioanna Giopanou
- Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio, Greece
- Antonia Marazioti
- Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio, Greece
- Vassilis Aidinis
- Institute of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Vari, Greece
- Rocio Sotillo
- ORCiD
- Division of Molecular Thoracic Oncology, Translational Lung Research Center (TLRC), German Cancer Research Center (DKFZ), The German Center for Lung Research (DZL), Heidelberg, Germany
- Georgios T Stathopoulos
- ORCiD
- Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio, Greece; Comprehensive Pneumology Center (CPC), Institute for Lung Biology and Disease (iLBD), University Hospital, Ludwig-Maximilians University, Helmholtz Center Munich, The German Center for Lung Research (DZL), Munich, Germany
- DOI
- https://doi.org/10.7554/eLife.45571
- Journal volume & issue
-
Vol. 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. 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.
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