Pluripotency-associated genes in human nasopharyngeal carcinoma CNE-2 cells are reactivated by a unique epigenetic sub-microenvironment

BMC Cancer

Research Article

Zhong-Min Dai¹  Ji-Yan Lin²  Zi-Jie Long³  Yu-Xin Cui⁴  Fei-Meng Zheng⁵  Yi-Xin Zeng⁵  Yi Liang⁵  Quentin Liu⁶  Jun-Xia Cao⁷ 

[1] College of Life Sciences, Zhejiang University, 388 Yuhangtang Road, 310058, Hangzhou, P.R. China;Department of Emergency, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Road, 510060, Guangzhou, P.R. China;Department of Hematology, Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, 510630, Guangzhou, P.R. China;Department of Pathology, University of Cambridge, Hills Road, BS2 0QQ, Cambridge, UK;State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, 650 Dongfeng Road, 510060, Guangzhou, P.R. China;State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, 650 Dongfeng Road, 510060, Guangzhou, P.R. China;Department of Hematology, Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, 510630, Guangzhou, P.R. China;State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, 650 Dongfeng Road, 510060, Guangzhou, P.R. China;The Jackson Laboratory, 600 Main Street, 04609, Bar Harbor, Maine, USA;

关键词: Cancer Stem Cell;    Subtraction Suppression Hybridization;    Side Population;    Side Population Cell;    Cancer Stem Cell Marker;   

DOI  :  10.1186/1471-2407-10-68

 received in 2009-08-24, accepted in 2010-02-25,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThere is increasing evidence that cancers contain their own stem-like cells, and particular attention has been paid to one subset of cancer-stem cells termed side population (SP). Stem cells under normal physical conditions are tightly controlled by their microenvironment, however, the regulatory role of the microenvironment surrounding cancer stem cells is not well characterized yet. In this study we found that the phenotype of SP can be "generated" by macrophage-like cells under conditioned culture. Furthermore the gene regulation pathway involved in cellular reprogramming process was investigated.MethodsThe selection and identification of SP in 50 CNE-2 single cell clones were performed by flow cytometry. The transwell assay and immunofluorescence staining were used to measure migration and cancer stem cell characters of non-SP single clone cells cultured with conditioned medium respectively. The subtraction suppression hybridization (SSH) technique and northern blotting analysis was applied to explore the pluripotency-associated genes under a unique epigenetic sub-microenvironment.ResultsAmong 50 clones, only one did not possess SP subpopulation while others did. The non-SP cells induced by macrophage-like cells showed more aggressive characters, which increased cell migration compared with the control cells and showed some fraction of SP phenotype. These cells expressed distinguished level of pluripotency-associated genes such as ADP-ribosylation factor-like 6 interacting protein (ARMER), poly (rC) binding protein 1 (PCBP1) and pyruvate dehydrogenase E1-β subunit (PDHB) when subjected to the environment.ConclusionTo our knowledge, this is the first study to demonstrate that non-SP single-clone cells can be induced to generate a SP phenotype when they are cultured with conditioned medium of macrophage-like cells, which is associated with the reactivation of pluripotency-associated genes.

【 授权许可】

CC BY   
© Cao et al; licensee BioMed Central Ltd. 2010