Presence of a putative tumor-initiating progenitor cell population predicts poor prognosis in smokers with non-small cell lung cancer.
Presence of a putative tumor-initiating progenitor cell population predicts poor prognosis in smokers with non-small cell lung cancer.
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DOI：
10.1158/0008-5472.can-10-0455
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发表时间：
2010-08-15
期刊：
影响因子：
11.2
通讯作者：
Gomperts BN
中科院分区：
文献类型：
--
作者：
Ooi AT;Mah V;Nickerson DW;Gilbert JL;Ha VL;Hegab AE;Horvath S;Alavi M;Maresh EL;Chia D;Gower AC;Lenburg ME;Spira A;Solis LM;Wistuba II;Walser TC;Wallace WD;Dubinett SM;Goodglick L;Gomperts BN
吸烟是肺癌发生的最重要的已知危险因素。烟草暴露导致慢性炎症、组织损伤和修复。最近的一个假说认为，干/祖细胞参与气道上皮修复，可能是肺癌的肿瘤起始细胞，并可能与复发和转移。我们使用免疫染色，定量实时PCR，Western印迹和肺癌组织微阵列，以确定气道上皮干/祖细胞亚群在稳态条件下，正常修复，异常修复与癌前病变和肺癌及其与损伤和预后的相关性。我们鉴定了一群角蛋白14（K14）表达的前体上皮细胞，它们参与损伤后的修复。在癌前病变的气道上皮中，失调的修复导致K14+细胞的持续存在。非小细胞肺癌（NSCLC）样本中K14+细胞的存在预测预后较差。这在吸烟者中尤其如此，其中NSCLC中K14+细胞的存在预示着转移。K14+祖气道上皮细胞在NSCLC中的存在预示着不良预后，并且这种预测值在吸烟者中最强，在吸烟者中也与转移相关。这表明，修复性K14+祖细胞可能是该吸烟者NSCLC亚组中的肿瘤起始细胞。
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 persistence of K14+ cells in the airway epithelium in premalignant lesions. The presence of K14+ cells in non-small cell lung cancer (NSCLC) samples predicted poorer outcomes. This was especially true in smokers where the presence of K14+ cells in NSCLC was predictive of metastasis. The presence of K14+ progenitor airway epithelial cells in NSCLC predicted a poor prognosis and this predictive value was strongest in smokers, where it also correlated with metastasis. This suggests that reparative K14+ progenitor cells may be tumor-initiating cells in this subgroup of smokers with NSCLC.