Kim Carla F Bender, Jackson Erica L, Woolfenden Amber E, Lawrence Sharon, Babar Imran, Vogel Sinae, Crowley Denise, Bronson Roderick T, Jacks Tyler
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Cell. 2005 Jun 17;121(6):823-35. doi: 10.1016/j.cell.2005.03.032.
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 bronchioalveolar 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.
损伤模型表明，肺中存在解剖学和功能上不同的上皮干细胞群。我们分离出了这样一种区域性肺干细胞群，称为支气管肺泡干细胞（BASCs）。BASCs在支气管肺泡导管连接处被识别，对细支气管和肺泡损伤具有抗性，并在体内上皮细胞更新过程中增殖。BASCs表现出自我更新能力，并且在克隆试验中具有多能性，突出了它们的干细胞特性。此外，BASCs在培养中对致癌性K-ras有反应，并在体内肺肿瘤前体细胞中扩增。这些数据支持这样的假设，即BASCs是维持远端肺的细支气管克拉拉细胞和肺泡细胞的干细胞群，并且它们的转化对应物会引发腺癌。尽管细支气管细胞和肺泡细胞被认为是腺癌的前体细胞，但这项研究指出BASCs是这种肺癌亚型的假定起源细胞。
