This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pegtel, D. M. Articles by Thorley-Lawson, D. A. Search for Related Content PubMed PubMed Citation Articles by Pegtel, D. M. Articles by Thorley-Lawson, D. A.

Epstein-Barr-Virus-Encoded LMP2A Induces Primary Epithelial Cell Migration and Invasion: Possible Role in Nasopharyngeal Carcinoma Metastasis

Department of Pathology, Tufts University School of Medicine, Jaharis Building, Boston, Massachusetts 02111,¹ Center for Genome Research, The Broad Institute of MIT and Harvard, 320 Charles Street, Cambridge, Massachusetts 02141-2023,² Department of Otolaryngology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan,³ Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan⁴

Received 23 August 2005/ Accepted 28 September 2005

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 (ITG6), 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 ITG6 RNA levels are up-regulated in epithelial cells expressing LMP2, and that ITG6 protein levels are increased in the migrating cells. Blocking antibodies against ITG6 abrogated LMP2-induced invasion through Matrigel by primary epithelial cells. Our results provide a link between LMP2A expression, ITG6 expression, epithelial cell migration, and NPC metastasis and suggest that EBV infection may contribute to the high incidence of metastasis in NPC progression.

Supplemental material for this article may be found at http://jvi.asm.org.

This article has been cited by other articles:

• Halasz, P., Holloway, G., Turner, S. J., Coulson, B. S. (2008). Rotavirus Replication in Intestinal Cells Differentially Regulates Integrin Expression by a Phosphatidylinositol 3-Kinase-Dependent Pathway, Resulting in Increased Cell Adhesion and Virus Yield. J. Virol. 82: 148-160 [Abstract] [Full Text]  
• Fukuda, M., Longnecker, R. (2007). Epstein-Barr Virus Latent Membrane Protein 2A Mediates Transformation through Constitutive Activation of the Ras/PI3-K/Akt Pathway. J. Virol. 81: 9299-9306 [Abstract] [Full Text]  
• Pegtel, D. M., Subramanian, A., Meritt, D., Tsai, C.-H., Sheen, T.-S., Golub, T. R., Thorley-Lawson, D. A. (2007). IFN-{alpha}-Stimulated Genes and Epstein-Barr Virus Gene Expression Distinguish WHO Type II and III Nasopharyngeal Carcinomas. Cancer Res. 67: 474-481 [Abstract] [Full Text]  
• Rovedo, M., Longnecker, R. (2007). Epstein-Barr Virus Latent Membrane Protein 2B (LMP2B) Modulates LMP2A Activity. J. Virol. 81: 84-94 [Abstract] [Full Text]  
• Sengupta, S., den Boon, J. A., Chen, I-H., Newton, M. A., Dahl, D. B., Chen, M., Cheng, Y.-J., Westra, W. H., Chen, C.-J., Hildesheim, A., Sugden, B., Ahlquist, P. (2006). Genome-Wide Expression Profiling Reveals EBV-Associated Inhibition of MHC Class I Expression in Nasopharyngeal Carcinoma. Cancer Res. 66: 7999-8006 [Abstract] [Full Text]