ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Open Biol. 2012 Aug;2(8):120094. doi: 10.1098/rsob.120094.
The isolation and characterization of lung stem and progenitor cells represent an important step towards the understanding of lung repair after injury, lung disease pathogenesis and the identification of the target cells of transformation in lung carcinogenesis. Different approaches using prospective isolation of progenitor cells by flow cytometry or lineage-tracing experiments in mouse models of lung injury have led to the identification of distinct progenitor subpopulations in different morphological regions of the adult lung. Genetically defined mouse models of lung cancer are offering new perspectives on the cells of origin of different subtypes of lung cancer. These mouse models pave the way to further investigate human lung progenitor cells at the origin of lung cancers, as well as to define the nature of the lung cancer stem cells. It will be critical to establish the link between oncogenic driver mutations recently discovered in lung cancers, target cells of transformation and subtypes of lung cancers to enable better stratification of patients for improved therapeutic strategies.
肺干细胞和祖细胞的分离和鉴定是理解肺损伤后的修复、肺病发病机制以及鉴定肺肿瘤发生中转化的靶细胞的重要步骤。使用流式细胞术对祖细胞进行前瞻性分离或在肺损伤的小鼠模型中进行谱系追踪实验等不同方法,已经在成年肺的不同形态区域中鉴定出不同的祖细胞亚群。肺癌的遗传定义小鼠模型为不同亚型肺癌的起源细胞提供了新的视角。这些小鼠模型为进一步研究起源于肺癌的人类肺祖细胞以及确定肺癌干细胞的性质铺平了道路。关键是要建立最近在肺癌中发现的致癌驱动突变、转化的靶细胞和肺癌亚型之间的联系,以便更好地对患者进行分层,从而制定出更好的治疗策略。