Thakur Chitra, Rapp Ulf R, Rudel Thomas
Cancer Metastasis Group, Department of Molecular Biology, Max Planck Institute of Biochemistry, Martinsried 82152, Germany.
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan 48201, USA.
Oncotarget. 2017 Dec 30;9(5):6518-6535. doi: 10.18632/oncotarget.23785. eCollection 2018 Jan 19.
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 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.
在肺癌治疗中，早期识别转移性肿瘤生长一直是最大的挑战之一。通过在小鼠非小细胞肺癌（NSCLC）条件模型中采用遗传谱系追踪方法，我们证明囊性病变代表转移性侵袭的早期阶段。我们构建了一个NSCLC小鼠模型，该模型在肺II型肺泡细胞中整合了由普遍存在的CAG启动子驱动的可遗传DsRed荧光标签。我们在次级器官（肝脏）中发现了早期囊性病变，这些病变缺乏肺标志物Scgb1a1和表面活性蛋白C（Sftpc）的表达，且DsRed呈阳性，从而确定肺为其起源。这证明了II型肺泡细胞在协调转移过程中的巨大潜力，使其成为人类NSCLC中具有治疗重要性的肺靶细胞类型之一。
