Functional analysis of EBV in nasopharyngeal carcinoma cells.
A membrane invasion culture system was used to study the ability of EBV to enhance invasion and migration of nasopharyngeal carcinoma (NPC) cells. Semi-reverse transcriptase-PCR analysis of matrix proteinases and angiogenic factors from EBV-infected, or EBV-positive (EBV+), cells demonstrated different degrees of elevated gene expression. In our animal model, EBV+ tumors grew faster and larger than EBV-free, or EBV-negative (EBV-), tumors and also had clonal EBV terminal repeat sequences. Double-localization of EBV and certain host proteins in EBV+ tumors and biopsy specimens demonstrated that EBV up-regulates host genes only in cells that express those genes but not in cells that do not express them. Double-localization of EBV and host genes in NPC biopsy specimens all showed EBV- tumor cells expressing those host genes. Our data strongly suggest that EBV infection enhances progression of NPC tumor growth. They do not rule out a role for EBV infection in the induction and early promotion of NPC development. Unidentified factors may also enhance NPC tumor growth independent of the effects of EBV.
Wu
Han-Chung
HC
National Taiwan University Hospital, and Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Lin
Yu-Ju
YJ
Lee
Jeng-Jie
JJ
Liu
Yung-Jung
YJ
Liang
Sung-Tzu
ST
Peng
Yet
Y
Chiu
Yung-Wen
YW
Wu
Chen-Wen
CW
Lin
Chin-Tarng
CT
D000818:Animals; D001706:Biopsy; D002277:Carcinoma / Q000473:pathology / Q000821:virology; D066246:ErbB Receptors / Q000032:analysis; D006133:Growth Substances / Q000032:analysis; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000473:pathology / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D066246:ErbB Receptors