Cancer Program Publication

EBV Encoded LMP2A Induces Primary Epithelial Cell Migration and Invasion  Possible Role in Nasopharyngeal Carcinoma Metastasis.
ProjectMetastasis
Additional Projects/
Categories
Cancer Susceptibility
Abstract 
Non-keratinizing 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 biopsies correlates with that of a cellular protein, Integrin-alpha-6 (ITGa6), 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 ITGa6 RNA levels are upregulated in epithelial cells expressing LMP2 and ITGa6 protein levels are increased in the migrating cells. Blocking antibodies against ITGa6 abrogated LMP2 induced invasion through Matrigel by primary epithelial cells. Our results provide a link between LMP2A expression, ITGa6 expression, epithelial cell migration and NPC metastasis and suggest that EBV infection may contribute to the high incidence of metastasis in NPC progression.
AuthorsDirk M. Pegtel, Aravind Subramanian, Tzung-Shiahn Sheen, Ching-Hwa Tsai, Todd R. Golub and David A. Thorley-Lawson
Publication Date10/01/2005
Contact emails david.thorley-lawson@tufts.edu
Publication URLhttp://www.broad.mit.edu/~aravind/tmp/pegtel.pdf
KeywordsMetastasis, EBV, LMP2A, NPC, GSEA