Yang Chun-Hung, Wang Hui-Ling, Lin Yi-Sheng, Kumar K P Shravan, Lin Hung-Chi, Chang Chih-Jung, Lu Chia-Chen, Huang Tsung-Teng, Martel Jan, Ojcius David M, Chang Yu-Sun, Young John D, Lai Hsin-Chih
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Division of Applied Toxicology, Taiwan Agricultural Chemicals and Toxic Substances Research Institute, Council of Agriculture, Executive Yuan, Taichung, Taiwan, Republic of China.
Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China.
PLoS One. 2014 Jun 23;9(6):e99412. doi: 10.1371/journal.pone.0099412. eCollection 2014.
Cancer stem cells (CSCs) represent a unique sub-population of tumor cells with the ability to initiate tumor growth and sustain self-renewal. Although CSC biomarkers have been described for various tumors, only a few markers have been identified for nasopharyngeal carcinoma (NPC). In this study, we show that CD24+ cells isolated from human NPC cell lines express stem cell genes (Sox2, Oct4, Nanog, Bmi-1, and Rex-1), and show activation of the Wnt/β-catenin signaling pathway. CD24+ cells possess typical CSC characteristics that include enhanced cell proliferation, increased colony and sphere formation, maintenance of cell differentiation potential in prolonged culture, and enhanced resistance to chemotherapeutic drugs. Notably, CD24+ cells produce tumors following inoculation of as few as 500 cells in immunodeficient NOD/SCID mice. CD24+ cells further show increased invasion ability in vitro, which correlates with enhanced expression of matrix metalloproteinase 2 and 9. In summary, our results suggest that CD24 represents a novel CSC biomarker in NPC.
癌症干细胞(CSCs)是肿瘤细胞中的一个独特亚群,具有启动肿瘤生长和维持自我更新的能力。尽管已经描述了多种肿瘤的癌症干细胞生物标志物,但鼻咽癌(NPC)仅鉴定出少数几种标志物。在本研究中,我们发现从人鼻咽癌细胞系中分离出的CD24+细胞表达干细胞基因(Sox2、Oct4、Nanog、Bmi-1和Rex-1),并显示Wnt/β-连环蛋白信号通路的激活。CD24+细胞具有典型的癌症干细胞特征,包括增强的细胞增殖、增加的集落和球体形成、在长期培养中维持细胞分化潜能以及增强对化疗药物的抗性。值得注意的是,在免疫缺陷的NOD/SCID小鼠中接种低至500个CD24+细胞即可产生肿瘤。CD24+细胞在体外还表现出增强的侵袭能力,这与基质金属蛋白酶2和9的表达增加相关。总之,我们的结果表明CD24是鼻咽癌中一种新的癌症干细胞生物标志物。