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Journal of Virology, December 2005, p. 15430-15442, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15430-15442.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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

Dirk M. Pegtel,1 Aravind Subramanian,2 Tzung-Shiahn Sheen,3 Ching-Hwa Tsai,4 Todd R. Golub,2 and David A. Thorley-Lawson1*

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 (ITG{alpha}6), 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 ITG{alpha}6 RNA levels are up-regulated in epithelial cells expressing LMP2, and that ITG{alpha}6 protein levels are increased in the migrating cells. Blocking antibodies against ITG{alpha}6 abrogated LMP2-induced invasion through Matrigel by primary epithelial cells. Our results provide a link between LMP2A expression, ITG{alpha}6 expression, epithelial cell migration, and NPC metastasis and suggest that EBV infection may contribute to the high incidence of metastasis in NPC progression.

* Corresponding author. Mailing address: Department of Pathology, Tufts University School of Medicine, Jaharis Building, 150 Harrison Ave., Boston, MA 02111. Phone: (617) 636-2726. Fax: (617) 636-2990. E-mail: david.thorley-lawson{at}tufts.edu.

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

Journal of Virology, December 2005, p. 15430-15442, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15430-15442.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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