Oncotarget

Research Papers:

Cysts mark the early stage of metastatic tumor development in non-small cell lung cancer

Chitra Thakur _, Ulf R. Rapp and Thomas Rudel

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Oncotarget. 2018; 9:6518-6535. https://doi.org/10.18632/oncotarget.23785

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Abstract

Chitra Thakur1,2, Ulf R. Rapp1,3 and Thomas Rudel4

1Cancer Metastasis Group, Department of Molecular Biology, Max Planck Institute of Biochemistry, Martinsried 82152, Germany

2Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan 48201, USA

3Department of Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Bad Nauheim 61231, Germany

4Department of Microbiology, Biocenter, University of Wuerzburg, Wuerzburg D-97074, Germany

Correspondence to:

Chitra Thakur, email: chitra.thakur@wayne.edu

Keywords: lung cancer; metastasis; cysts; lineage tracing; dedifferentiation

Received: August 19, 2017     Accepted: December 24, 2017     Published: December 30, 2017

ABSTRACT

Identifying metastatic tumor growth at an early stage has been one of the biggest challenges in the treatment of lung cancer. By genetic lineage tracing approach in a conditional model of Non-Small Cell Lung Cancer (NSCLC) in mice, we demonstrate that cystic lesions represent an early stage of metastatic invasion. We generated a mouse model for NSCLC which incorporated a heritable DsRed fluorescent tag driven by the ubiquitous CAG promoter in the alveolar type II cells of the lung. We found early cystic lesions in a secondary organ (liver) that lacked the expression of bona fide lung makers namely Scgb1a1 and surfactant protein C Sftpc and were DsRed positive hence identifying lung as their source of origin. This demonstrates the significant potential of alveolar type II cells in orchestrating the process of metastasis, rendering it as one of the target cell types of the lung of therapeutic importance in human NSCLC.


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