Publication in refereed journal
香港中文大学研究人员 ( 现职)
| 伦慧敏博士 (化学病理学系) |
| 周捷博士 (病理解剖及细胞学系) |
| 罗国炜教授 (病理解剖及细胞学系) |
| 吴香玲教授 (病理解剖及细胞学系) |
| 高振威先生 |
| 锺天恩博士 (化学病理学系) |
| 蔡光伟教授 (妇产科学系) |
| 杜家辉教授 (病理解剖及细胞学系) |
全文
| 数位物件识别号 (DOI) http://dx.doi.org/10.1371/journal.pone.0052426 |
引用次数
Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/30WOS source URL
其它资讯
摘要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.
着者Lun SWM, Cheung ST, Cheung PFY, To KF, Woo JKS, Choy KW, Chow C, Cheung CCM, Chung GTY, Cheng ASH, Ko CW, Tsao SW, Busson P, Ng MHL, Lo KW
期刊名称PLoS ONE
出版年份2012
月份12
日期21
卷号7
期次12
出版社PUBLIC LIBRARY SCIENCE
国际标準期刊号1932-6203
语言英式英语
Web of Science 学科类别Multidisciplinary Sciences; MULTIDISCIPLINARY SCIENCES; Science & Technology - Other Topics
