Department of Pediatrics, Division of Hematology Oncology, Mattel Children's Hospital, University of California at Los Angeles, David Geffen School of Medicine at the University of California, Los Angeles, California, USA.
Cancer Res. 2010 Aug 15;70(16):6639-48. doi: 10.1158/0008-5472.CAN-10-0455.
Smoking is the most important known risk factor for the development of lung cancer. Tobacco exposure results in chronic inflammation, tissue injury, and repair. A recent hypothesis argues for a stem/progenitor cell involved in airway epithelial repair that may be a tumor-initiating cell in lung cancer and which may be associated with recurrence and metastasis. We used immunostaining, quantitative real-time PCR, Western blots, and lung cancer tissue microarrays to identify subpopulations of airway epithelial stem/progenitor cells under steady-state conditions, normal repair, aberrant repair with premalignant lesions and lung cancer, and their correlation with injury and prognosis. We identified a population of keratin 14 (K14)-expressing progenitor epithelial cells that was involved in repair after injury. Dysregulated repair resulted in the persistence of K14+ cells in the airway epithelium in potentially premalignant lesions. The presence of K14+ progenitor airway epithelial cells in NSCLC predicted a poor prognosis, and this predictive value was strongest in smokers, in which it also correlated with metastasis. This suggests that reparative K14+ progenitor cells may be tumor-initiating cells in this subgroup of smokers with NSCLC.
吸烟是导致肺癌发生的最重要的已知危险因素。烟草暴露会导致慢性炎症、组织损伤和修复。最近的一个假说认为，气道上皮修复中涉及的干细胞/祖细胞可能是肺癌的起始细胞，并且可能与复发和转移有关。我们使用免疫染色、定量实时 PCR、Western blot 和肺癌组织微阵列来鉴定在稳态条件、正常修复、具有癌前病变和肺癌的异常修复下气道上皮干细胞/祖细胞的亚群，并研究它们与损伤和预后的相关性。我们鉴定了一个表达角蛋白 14 (K14)的祖细胞上皮细胞群，该细胞群参与损伤后的修复。失调的修复导致潜在癌前病变中气道上皮中 K14+细胞的持续存在。非小细胞肺癌 (NSCLC) 中存在 K14+祖细胞气道上皮细胞预示着预后不良，而在吸烟者中这种预测价值更强，并且它也与转移相关。这表明，在这组吸烟的 NSCLC 患者中，修复性的 K14+祖细胞可能是起始细胞。
