Abstract
Epstein‐Barr virus (EBV)‐associated undifferentiated nasopharyngeal carcinoma (NPC) is characterized by a prominent nonneoplastic lymphoid stroma. The functional role of these inflammatory cells and the mechanism of their recruitment are not fully understood. In B‐cells, the EBV‐encoded latent membrane protein 1 (LMP1) can induce the expression of chemokines in an NF‐κB dependent manner. We now show that LMP1 can induce the expression of RANTES and MCP‐1 in an epithelial cell line, and that this effect is partially reversible by an inhibitor of NF‐κB. Since tumor cells of virtually all NPCs show CD40 expression while many cases are LMP1‐negative at the protein level, we also investigated the effect of CD40 signaling and demonstrate that CD40 stimulation can transiently induce RANTES and MCP‐1 expression in LMP1‐negative epithelial cells. In in situ hybridization only rare tumor cells showed expression of these chemokines unrelated to LMP1 expression, a pattern consistent with transient induction through CD40 signaling. Since RANTES and MCP‐1 were also detected in the neoplastic cells of oral squamous cell carcinomas lacking a lymphoid stroma it remains uncertain to what extent these CC chemokines contribute to the attraction of inflammatory cells into the NPC microenvironment. © 2007 Wiley‐Liss, Inc.