Identification of bronchioalveolar stem cells in normal lung and lung cancer
Identification of bronchioalveolar stem cells in normal lung and lung cancer
复制标题
DOI：
10.1016/j.cell.2005.03.032
复制
发表时间：
2005-06-17
期刊：
影响因子：
64.5
通讯作者：
Jacks, T
中科院分区：
文献类型：
--
作者：
Kim, CFB;Jackson, EL;Jacks, T
损伤模型表明，肺包含解剖学和功能上不同的上皮干细胞群。我们已经分离出这样一个区域性的肺干细胞群，称为支气管肺泡干细胞（BASCs）。在细支气管肺泡管连接处鉴定，BASCs对细支气管和肺泡损伤具有抗性，并在体内上皮细胞更新期间增殖。BASCs表现出自我更新，在克隆试验中是多能的，突出了它们的干细胞特性。此外，BASCs在培养物和体内肺肿瘤前体中对致癌K-ras的反应中扩增。这些数据支持以下假设：BASC是维持远端肺的细支气管Clara细胞和肺泡细胞的干细胞群，并且它们的转化对应物产生腺癌。虽然细支气管细胞和肺泡细胞被认为是腺癌的前体细胞，但这项工作指出BASC是这种肺癌亚型的假定起源细胞。
Injury models have suggested that the lung contains anatomically and functionally distinct epithelial stem cell populations. We have isolated such a regional pulmonary stem cell population, termed bronchloalveolar stem cells (BASCs). Identified at the bronchioalveolar duct junction, BASCs were resistant to bronchiolar and alveolar damage and proliferated during epithelial cell renewal in vivo. BASCs exhibited self-renewal and were multipotent in clonal assays, highlighting their stem cell properties. Furthermore, BASCs expanded in response to oncogenic K-ras in culture and in precursors of lung tumors in vivo. These data support the hypothesis that BASCs are a stem cell population that maintains the bronchiolar Clara cells and alveolar cells of the distal lung and that their transformed counterparts give rise to adenocarcinoma. Although bronchiolar cells and alveolar cells are proposed to be the precursor cells of adenocarcinoma, this work points to BASCs as the putative cells of origin for this subtype of lung cancer.