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


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Article

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Authors

Cao, Jun-Xia 
Cui, Yu-Xin 
Long, Zi-Jie 
Dai, Zhong-Min 
Lin, Ji-Yan 

Abstract

BACKGROUND: There 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. METHODS: The 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. RESULTS: Among 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-beta subunit (PDHB) when subjected to the environment. CONCLUSION: To 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.

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RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.

Keywords

Carcinoma, Cell Culture Techniques, Cell Line, Tumor, Cell Movement, Cell Separation, Culture Media, Conditioned, Epigenesis, Genetic, Flow Cytometry, Humans, Macrophages, Microscopy, Fluorescence, Nasopharyngeal Neoplasms, Neoplasm Transplantation, Neoplastic Stem Cells, Nucleic Acid Hybridization

Journal Title

BMC Cancer

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Journal ISSN

1471-2407
1471-2407

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Publisher

Springer Science and Business Media LLC