Molecular events associated with epithelial to mesenchymal transition of nasopharyngeal carcinoma cells in the absence of Epstein-Barr virus genomeReportar como inadecuado




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Journal of Biomedical Science

, 16:105

First Online: 24 November 2009Received: 23 June 2009Accepted: 24 November 2009DOI: 10.1186-1423-0127-16-105

Cite this article as: Lin, JC., Liao, SK., Lee, EH. et al. J Biomed Sci 2009 16: 105. doi:10.1186-1423-0127-16-105

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.

AbbreviationsMMPmatrix metalloproteinase

TPA12-O-tetradecanyol-phorbol-13-acetate

VEGFvascular endothelial growth factor

EMTepithelial-mesenchymal transition

EBVEpstein-Barr virus

LMP-1latent membrane protein-1.

Electronic supplementary materialThe online version of this article doi:10.1186-1423-0127-16-105 contains supplementary material, which is available to authorized users.

Jung-Chung Lin, Shuen-Kuei Liao contributed equally to this work.

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Autor: Jung-Chung Lin - Shuen-Kuei Liao - En-Huei Lee - Man-Shan Hung - Yiyang Sayion - Hung-Chang Chen - Chen-Chen Kang - Liang-S

Fuente: https://link.springer.com/







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