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J Virol DOI:10.1128/JVI.79.24.15430-15442.2005

Epstein-Barr-virus-encoded LMP2A induces primary epithelial cell migration and invasion: possible role in nasopharyngeal carcinoma metastasis.

Publication TypeJournal Article
Year of Publication2005
AuthorsPegtel, DM, Subramanian, A, Sheen, T-S, Tsai, C-H, Golub, TR, Thorley-Lawson, DA
JournalJ Virol
Date Published2005 Dec
KeywordsCell Line, Cell Movement, Epithelial Cells, Gene Expression Regulation, Viral, Genes, Viral, Herpesvirus 4, Human, Humans, Nasopharyngeal Neoplasms, Nasopharynx, Neoplasm Metastasis, Viral Matrix Proteins

Nonkeratinizing nasopharyngeal carcinomas (NPC) are >95% associated with the expression of the Epstein-Barr virus (EBV) LMP2A latent protein. However, the role of EBV, in particular, LMP2A, in tumor progression is not well understood. Using Affymetrix chips and a pattern-matching computational technique (neighborhood analysis), we show that the level of LMP2A expression in NPC biopsy samples correlates with that of a cellular protein, integrin-alpha-6 (ITGalpha6), that is associated with cellular migration in vitro and metastasis in vivo. We have recently developed a primary epithelial model from tonsil tissue to study EBV infection in epithelial cells. Here we report that LMP2A expression in primary tonsil epithelial cells causes them to become migratory and invasive, that ITGalpha6 RNA levels are up-regulated in epithelial cells expressing LMP2, and that ITGalpha6 protein levels are increased in the migrating cells. Blocking antibodies against ITGalpha6 abrogated LMP2-induced invasion through Matrigel by primary epithelial cells. Our results provide a link between LMP2A expression, ITGalpha6 expression, epithelial cell migration, and NPC metastasis and suggest that EBV infection may contribute to the high incidence of metastasis in NPC progression.


Alternate JournalJ. Virol.
PubMed ID16306614
PubMed Central IDPMC1316046
Grant ListR01 AI018757 / AI / NIAID NIH HHS / United States
R01 CA065883 / CA / NCI NIH HHS / United States
AI 18757 / AI / NIAID NIH HHS / United States
CA 65883 / CA / NCI NIH HHS / United States