Hypoxia-induced cell stemness leads to drug resistance and poor prognosis in lung adenocarcinoma
Hypoxia-induced cell stemness leads to drug resistance and poor prognosis in lung adenocarcinoma
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DOI：
10.1016/j.lungcan.2014.11.017
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发表时间：
2015-02-01
期刊：
影响因子：
5.3
通讯作者：
Zhou, Caicun
中科院分区：
文献类型：
--
作者：
Zhao, Mingchuan;Zhang, Yishi;Zhou, Caicun
背景资料：由于肿瘤干细胞具有胚胎样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。癌细胞的干性也与缺氧环境中的癌症高度相关。方法：在我们的研究中，我们使用二氯化钴（CoCl 2）为肺腺癌A549细胞和顺铂耐药细胞系A549/DDP创造缺氧环境。经磁性抗体分离后，流式细胞仪和实时荧光定量PCR检测肿瘤干细胞样CD 166阳性细胞群和干细胞性。还测量了顺铂、多西他赛和培美曲塞的耐药性。最后，组织芯片被用来分析缺氧诱导的干细胞和根治性surgery.Results后的总体生存率之间的关系：数据显示，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细胞干细胞。CD 166阳性的癌干细胞样群体比CD 166阴性的细胞表现出更大的耐药性。组织阵列研究还表明，组织表达较高CD 166水平的患者预后较差。结论：我们的研究结果表明，化学缺氧可能会增加癌细胞的干性和CD 166阳性干细胞的耐药性。因此，靶向干细胞样细胞群，特别是CD 166阳性细胞，可能代表治疗肺癌的新治疗策略。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Background: 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 sternness is also highly relevant to cancer in hypoxic environments.Methods: 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' sternness 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.Results: Data showed that chemical-induced hypoxia changed cell sternness by enhancing stem cell transcription factors and markers of chemotherapeutic drug resistance. The CD166-positive cancer stern 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.Conclusion: Our findings indicate that chemical hypoxia may augment cancer cell sternness and drug resistance in CD166-positive stern cells. Therefore, targeting the stem-like cell population, especially CD166-positive cells, may represent a novel therapeutic strategy to treat lung cancer. (C) 2014 Elsevier Ireland Ltd. All rights reserved.