CD44+ cancer stem-like cells in EBV-associated nasopharyngeal carcinoma.
CD44+ cancer stem-like cells in EBV-associated nasopharyngeal carcinoma.
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CD44+与EBV相关的鼻咽癌中的癌症干细胞。
DOI：
10.1371/journal.pone.0052426
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lo KW
中科院分区：
文献类型：
--
作者：
Lun SW;Cheung ST;Cheung PF;To KF;Woo JK;Choy KW;Chow C;Cheung CC;Chung GT;Cheng AS;Ko CW;Tsao SW;Busson P;Ng MH;Lo KW
鼻咽癌（Nasopharyngeal carcinoma，NPC）是一种独特的EB病毒相关上皮性恶性肿瘤，具有高度侵袭性和转移性。尽管越来越多的证据表明癌症干细胞样细胞（CSC）在各种恶性肿瘤的维持和进展中起着关键作用，但在EBV相关NPC中CSC的存在和性质在很大程度上是未知的。我们的研究旨在阐明CSC在这种恶性疾病的发病机制中的存在和作用。从EBV阳性的NPC细胞系C666-1中分离出球形形成细胞，并通过体外和体内试验证实其肿瘤起始特性。流式细胞仪检测结果表明，在大多数球形C666-1细胞中，CD 44和SOX 2均过表达。在EBV阳性异种移植物和原发性肿瘤中的少数群体中检测到CD 44 + SOX 2+细胞，并将其视为NPC中的潜在CSC。值得注意的是，分离的CD 44 + NPC细胞对化疗剂具有抗性，并且具有更高的球体形成效率，显示出CSC特性。另一方面，微阵列分析已经揭示了许多差异表达的基因，这些基因涉及球状体中的转录调节（例如FOXN 4、GLI 1）、免疫应答（CCR 7、IL 8）和跨膜转运（例如ABCC 3、ABCC 11）。在这些基因中，在NPC异种移植物和原发性肿瘤中证实了CD 44 + CSC中CCR 7的表达增加。重要的是，阻断CCR 7可在体外消除C666-1的成球能力。CCR 7的表达与复发和远处转移有关。目前的研究确定了EBV相关NPC中CSC亚群的特定性质。我们的研究结果为开发针对CSC的有效疗法提供了新的见解，从而增强了NPC患者的治疗效果。
Nasopharyngeal carcinoma (NPC) is a unique EBV-associated epithelial malignancy, showing highly invasive and metastatic phenotype. Despite increasing evidence demonstrating the critical role of cancer stem-like cells (CSCs) in the maintenance and progression of tumors in a variety of malignancies, the existence and properties of CSC in EBV-associated NPC are largely unknown. Our study aims to elucidate the presence and role of CSCs in the pathogenesis of this malignant disease. Sphere-forming cells were isolated from an EBV-positive NPC cell line C666-1 and its tumor-initiating properties were confirmed by in vitro and in vivo assays. In these spheroids, up-regulation of multiple stem cell markers were found. By flow cytometry, we demonstrated that both CD44 and SOX2 were overexpressed in a majority of sphere-forming C666-1 cells. The CD44+SOX2+ cells was detected in a minor population in EBV-positive xenografts and primary tumors and considered as potential CSC in NPC. Notably, the isolated CD44+ NPC cells were resistant to chemotherapeutic agents and with higher spheroid formation efficiency, showing CSC properties. On the other hand, microarray analysis has revealed a number of differentially expressed genes involved in transcription regulation (e.g. FOXN4, GLI1), immune response (CCR7, IL8) and transmembrane transport (e.g. ABCC3, ABCC11) in the spheroids. Among these genes, increased expression of CCR7 in CD44+ CSCs was confirmed in NPC xenografts and primary tumors. Importantly, blocking of CCR7 abolished the sphere-forming ability of C666-1 in vitro. Expression of CCR7 was associated with recurrent disease and distant metastasis. The current study defined the specific properties of a CSC subpopulation in EBV-associated NPC. Our findings provided new insights into developing effective therapies targeting on CSCs, thereby potentiating treatment efficacy for NPC patients.
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影响因子：
2.5
作者：
Dean, Michael
通讯作者：
Dean, Michael
影响因子：
4.8
作者：
Bussolati, Benedetta;Bruno, Stefania;Camussi, Giovanni
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Camussi, Giovanni
表达 CD44 的非小细胞肺癌细胞富含干细胞样特性。
影响因子：
3.7
作者：
Leung, Elaine Lai-Han;Fiscus, Ronald R.;Tung, James W.;Tin, Vicky Pui-Chi;Cheng, Lik Cheung;Sihoe, Alan Dart-Loon;Fink, Louis M.;Ma, Yupo;Wong, Maria Pik
通讯作者：
Wong, Maria Pik
影响因子：
4.2
作者：
Mine T;Matsueda S;Gao H;Li Y;Wong KK;Peoples GE;Ferrone S;Ioannides CG
通讯作者：
Ioannides CG
影响因子：
11.2
作者：
Liu, Jeff C.;Deng, Tao;Zacksenhaus, Eldad
通讯作者：
Zacksenhaus, Eldad