Molecular events associated with epithelial to mesenchymal transition of nasopharyngeal carcinoma cells in the absence of Epstein-Barr virus genome.
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 beta-catenin with concomitant increased expression of Ets1. NPC-BM29 cells expressed >or= 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-1alpha 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.
Lin
Jung-Chung
JC
Department of Internal Medicine, Chung Shan Medical University Hospital/Chung Shan Medical University, Taichung, Taiwan. jxl8@cdc.gov
Liao
Shuen-Kuei
SK
Lee
En-Huei
EH
Hung
Man-Shan
MS
Sayion
Yiyang
Y
Chen
Hung-Chang
HC
Kang
Chen-Chen
CC
Huang
Liang-Sheng
LS
Cherng
Jaw-Ming
JM
D001706:Biopsy; D001854:Bone Marrow Cells / Q000473:pathology / Q000821:virology; D002277:Carcinoma / Q000821:virology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004848:Epithelium / Q000821:virology; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D008648:Mesoderm / Q000821:virology; D009303:Nasopharyngeal Neoplasms / Q000821:virology*; D009362:Neoplasm Metastasis; D010641:Phenotype; D014945:Wound Healing