Coxsackie-adenovirus receptor as a novel marker of stem cells in treatment-resistant non-small cell lung cancer.
Coxsackie-adenovirus receptor as a novel marker of stem cells in treatment-resistant non-small cell lung cancer.
复制标题
DOI：
10.1016/j.radonc.2012.09.002
复制
发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Chang JY
中科院分区：
文献类型：
--
作者：
Zhang X;Fang B;Mohan R;Chang JY
由于肿瘤干细胞(CSCs)的存在而导致的治疗耐药性仍然是癌症治疗中的一个挑战。对耐药非小细胞肺癌(NSCLC)中CSCs的可能标记物知之甚少。我们探索了柯萨奇和腺病毒受体(CAR)作为治疗耐药非小细胞肺癌模型中CSCs的标志物之一。通过紫杉醇或分次照射建立耐药细胞系H460和A549。免疫印迹和流式细胞仪检测CSC标志物。我们还建立了稳定的CAR过表达和稳定的shRNA-CAR基因敲除细胞系，并通过克隆形成、端粒酶、Matrigel和肿瘤形成实验评估了它们的存活率、侵袭力和致瘤能力。在体外和体内，Car的表达与CSC的表型有关。与亲本细胞相比，过度表达CAR的细胞具有更强的抗药性、自我更新和致瘤性，而shRNA介导的CAR表达下调足以抑制这些功能。CAR的表达也与上皮-间充质转化有关。我们首次证明CAR是CSCs的标志物，并可能影响耐药NSCLC中CSCs的活性。CAR可能被证明是非小细胞肺癌患者CSC治疗的靶点和治疗反应的预测指标。
Treatment resistance resulting from the presence of cancer stem cells (CSCs) remains a challenge in cancer treatment. Little is known about possible markers of CSCs in treatment-resistant non-small cell lung cancer (NSCLC). We explored the coxsackie- and adenovirus receptor (CAR) as one such marker of CSCs in models of treatment-resistant NSCLC. Resistant H460 and A549 cell lines were established by repeated exposure to paclitaxel or fractionated radiation. CSC markers were measured by western blotting and flow cytometry. We also established stable CAR-overexpressing and stable shRNA-CAR-knockdown cell lines and assessed their survival, invasiveness, and tumorigenic capabilities with clonogenic, telomerase, Matrigel, and tumor formation assays. CAR expression was associated with CSC phenotype both in vitro and in vivo. CAR-overexpressing cells were more treatment-resistant, self-renewing, and tumorigenic than were parental cells, and shRNA-mediated knockdown of CAR expression was sufficient to inhibit these functions. CAR expression also correlated with the epithelial-mesenchymal transition. We showed for the first time that CAR is a marker of CSCs and may affect the activities of CSCs in treatment-resistant NSCLC. CAR may prove to be a target for CSC treatment and a predictor of treatment response in patients with NSCLC.
登录
查看更多内容
影响因子：
11.5
作者：
Brüning, A;Stickeler, E;Runnebaum, IB
通讯作者：
Runnebaum, IB
影响因子：
4
作者：
Dorner, AA;Wegmann, F;Vestweber, D
通讯作者：
Vestweber, D
影响因子：
12.4
作者：
Eramo, A.;Lotti, F.;De Maria, R.
通讯作者：
De Maria, R.
影响因子：
11.2
作者：
Li, Chenwei;Heidt, David G.;Simeone, Diane M.
通讯作者：
Simeone, Diane M.
影响因子：
11.2
作者：
Collins, AT;Berry, PA;Maitland, NJ
通讯作者：
Maitland, NJ