Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Oncology, Fuda Hospital, School of Medicine, Jinan University, Guangzhou, China.
Lung Cancer. 2015 Feb;87(2):98-106. doi: 10.1016/j.lungcan.2014.11.017. Epub 2014 Dec 3.
Since cancer stem cells exhibit embryonic-like self-renewal characteristics and malignant behavior, including drug resistance and metastasis, they may be the origin of tumorigenesis and cancer recurrence. Cancer cell stemness is also highly relevant to cancer in hypoxic environments.
In our study, we used cobalt dichloride (CoCl2) to create a hypoxic environment for lung adenocarcinoma A549 cells and the cisplatine-resistant cell line A549/DDP. The cancer stem-like CD166 positive population and the cells' stemness were detected by flowcytometry and quantitative real-time PCR after separation using magnetic antibodies. Drug resistance to cisplatine, docetaxel and pemetrexed was also measured. Finally, a tissue array was used to analyze the relationship between hypoxia-induced stemness and overall survival after radical surgery.
Data showed that chemical-induced hypoxia changed cell stemness by enhancing stem cell transcription factors and markers of chemotherapeutic drug resistance. The CD166-positive cancer stem cell-like population showed greater drug resistance than the CD166-negative cells. Tissue array studies also suggested a poorer prognosis for patients whose tissue expressed higher CD166 levels.
Our findings indicate that chemical hypoxia may augment cancer cell stemness and drug resistance in CD166-positive stem cells. Therefore, targeting the stem-like cell population, especially CD166-positive cells, may represent a novel therapeutic strategy to treat lung cancer.
由于癌症干细胞具有类似胚胎的自我更新特性和恶性行为，包括耐药性和转移，它们可能是肿瘤发生和癌症复发的起源。癌症干细胞的干性也与缺氧环境中的癌症高度相关。
在我们的研究中，我们使用氯化钴（CoCl2）在肺腺癌 A549 细胞和顺铂耐药细胞系 A549/DDP 中创建缺氧环境。使用磁性抗体分离后，通过流式细胞术和实时定量 PCR 检测 CD166 阳性的癌症干细胞样群体和细胞干性。还测量了对顺铂、多西他赛和培美曲塞的耐药性。最后，使用组织阵列分析根治性手术后缺氧诱导的干性与总生存之间的关系。
数据表明，化学诱导的缺氧通过增强干细胞转录因子和化疗药物耐药标志物改变了细胞干性。CD166 阳性的癌症干细胞样群体比 CD166 阴性细胞表现出更强的耐药性。组织阵列研究还表明，组织中表达较高 CD166 水平的患者预后较差。
我们的研究结果表明，化学缺氧可能增强 CD166 阳性干细胞中的癌症细胞干性和耐药性。因此，针对类干细胞群体，特别是 CD166 阳性细胞，可能代表治疗肺癌的一种新的治疗策略。
