Molecular events associated with epithelial to mesenchymal transition of nasopharyngeal carcinoma cells in the absence of Epstein-Barr virus genome |
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Authors: | Jung-Chung Lin Shuen-Kuei Liao En-Huei Lee Man-Shan Hung Yiyang Sayion Hung-Chang Chen Chen-Chen Kang Liang-Sheng Huang Jaw-Ming Cherng |
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Institution: | (1) Laboratory Branch, Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, Georgia, USA;(2) Graduate Institutes of Clinical Medical Sciences and Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan;(3) Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan;(4) AsiaGen, Southern Taiwan Science Park, Tainan, Taiwan;(5) Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan;(6) Department of Internal Medicine, Chung Shan Medical University Hospital/Chung Shan Medical University, 110, Jianguo N Road, Sec 1, Taichung, Taiwan |
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Abstract: | Epithelial-mesenchymal transition (EMT) is an important process in tumor metastasis. The EMT-related events associated with
metastasis of NPC in the absence of EBV have not been elucidated. We established an EBV-negative NPC cell line from a bone
marrow biopsy of an NPC patient. Using a Matrigel system we isolated an invasive and non-invasive sublines, designated NPC-BM29
and NPC-BM00. NPC-BM29 acquired an invasive-like phenotype characterized by EMT, marked by down-regulation of E-cadherin and
β-catenin with concomitant increased expression of Ets1. NPC-BM29 cells expressed ≥ 10-fold higher of MMP-9 than NPC-BM00
cells. NPC-BM29 cells grew better in 2% serum than NPC-BM00 cells, with a population doubling-time of 26.8 h and 30.7 h, respectively.
A marked reduction in colony-formation ability of NPC-BM00 cells compared to NPC-BM29 was observed. Wound-healing assay revealed
that NPC-BM29 cells displayed higher motility than NPC-BM00 and the motility was further enhanced by cell treatment with TPA,
a PKC activator. Cell surface markers and tumor-associated molecules, AE3, MAK6 and sialyl-Tn, were up-regulated in NPC-BM29
cells, whereas the expression of HLA-DR and CD54 was significantly increased in NPC-BM00 cells. NPC-BM29 consistently released
higher levels of IL-8 and IL-10 than NPC-BM00, with low levels of IL-1α expression in both cell lines. Higher level of VEGF
production was detected in NPC-BM00 than NPC-BM29 cells. These data show that EBV is not required for exhibiting multiple
metastatic phenotypes associated with EMT. More studies that target right molecules/signalings associated with the EMT may
offer new therapeutic intervention options for NPC invasion and metastasis. |
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