Alveolar type II cells possess the capability of initiating lung tumor development.
Alveolar type II cells possess the capability of initiating lung tumor development.
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DOI：
10.1371/journal.pone.0053817
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chuang PT
中科院分区：
文献类型：
--
作者：
Lin C;Song H;Huang C;Yao E;Gacayan R;Xu SM;Chuang PT
鉴定肿瘤起源细胞是肿瘤生物学的一个基本问题。这个核心问题的答案不仅将促进我们对肿瘤发生和发展的理解，而且具有重要的治疗意义。在这项研究中，我们旨在揭示肺腺癌的起源细胞，肺腺癌是非小细胞肺癌的主要亚型。为此，我们开发了新的肺腺癌小鼠模型，该模型能够选择性地操纵表面活性剂相关蛋白C （SPC）表达细胞的基因活性，包括肺泡II型细胞和位于细支气管肺泡管交界处（BADJ）的细支气管肺泡干细胞（BASCs）。我们的研究结果表明，在SPC+细胞中单独激活致癌Kras或联合去除肿瘤抑制因子p53可导致肺泡肿瘤的发生。同样，SPC+细胞中持续的EGF信号传导导致肺泡肿瘤。相比之下，在这些条件下，BASCs不能增殖或产生肿瘤。重要的是，在一种小鼠品系中，Kras/p53活性在II型细胞中选择性改变，而在BASCs中不改变，肺泡肿瘤发生，而badj保持正常结构。这些结果证实并扩展了先前的发现，并支持肺腺癌可以在肺泡II型细胞中开始的模型。我们的结果为阐明肺癌在特定肺细胞类型中发生和发展的分子机制奠定了基础。
Identifying cells of tumor origin is a fundamental question in tumor biology. Answers to this central question will not only advance our understanding of tumor initiation and progression but also have important therapeutic implications. In this study, we aimed to uncover the cells of origin of lung adenocarcinoma, a major subtype of non-small cell lung cancer. To this end, we developed new mouse models of lung adenocarcinoma that enabled selective manipulation of gene activity in surfactant associated protein C (SPC)-expressing cells, including alveolar type II cells and bronchioalveolar stem cells (BASCs) that reside at the bronchioalveolar duct junction (BADJ). Our findings showed that activation of oncogenic Kras alone or in combination with the removal of the tumor suppressor p53 in SPC+ cells resulted in development of alveolar tumors. Similarly, sustained EGF signaling in SPC+ cells led to alveolar tumors. By contrast, BASCs failed to proliferate or produce tumors under these conditions. Importantly, in a mouse strain in which Kras/p53 activity was selectively altered in type II cells but not BASCs, alveolar tumors developed while BADJs retained normal architecture. These results confirm and extend previous findings and support a model in which lung adenocarcinoma can initiate in alveolar type II cells. Our results establish the foundation for elucidating the molecular mechanisms by which lung cancer initiates and progresses in a specific lung cell type.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
DOI：
10.1073/pnas.101500298
发表时间：
2001-05-22
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
64.5
作者：
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通讯作者：
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影响因子：
30.8
作者：
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通讯作者：
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