The Role Of Il-6/Stat3 Axis In The Transformation Of Epstein-Barr Virus (Ebv) Infected-Immortalized Nasopharyngeal Epithelial Cells

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC The role of IL-6/STAT3 axis in the transformation of Epstein-Barr Virus (EBV) infected-immortalized nasopharyngeal epithelial cells. Zhang Guitao, Tsang Chi Man, Chen Honglin, Tsao Sai Wah. Nasopharyngeal carcinoma (NPC) is rare throughout most parts of the world but common in certain geographic area, such as Southern China including Hong Kong. The etiology is based on intricate interactions among environmental factors, genetic susceptibility and Epstein-Barr virus (EBV) infection. Elevated antibody titers to EBV antigens are regularly observed in NPC patients. However, little information is available concerning the role of EBV in the early stage of NPC carcinogenesis. Our laboratory has established and characterized immortalized nasopharyngeal epithelial cells lines as premalignant nasopharyngeal cell models to examine for the transformation property of EBV infection in early stage of NPC development. Our results show that EBV infection activates STAT3 in immortalized nasopharyngeal epithelial cells. We had previously reported that the EBV-encoded LMP1 could upregulate IL-6 secretion to activate STAT3 signaling. Interestingly, we observed that activation of STAT3 in EBV-infected immortalized nasopharyngeal epithelial cells is highly susceptible to the induction by inflammatory cytokines, notably IL-6. Using quantitative real-time PCR, up-regulation of LMP1 was observed after IL-6 treatment on a time course dependent manner. An analysis of IL-6 receptor (IL-6R) indicated that EBV-infected nasopharyngeal epithelial cells have elevated level of IL-6R expression compared with uninfected cells. Activation of STAT3 signaling in immortalized nasopharyngeal epithelial cells by expressing a flag-tagged constitutively active STAT3-C confers transformed properties to cells. Our results support a model that EBV infection may predispose the aberrant STAT3 signaling for inflammatory cytokines involving the activation of LMP1/IL-6/STAT3 axis in premalignant nasopharyngeal epithelial cells. Enhanced STAT3 activation in EBV-infected epithelial cells by stromal inflammatory cytokines could result in irregular-gene expressions and cell signaling essential for malignant transformation, which may represent a crucial function of EBV infection in the development of nasopharyngeal carcinoma. (This project is supported by The Research Grant Council (Hong Kong) and Area of Excellence on Nasopharyngeal Carcinoma Research Center (Hong Kong)). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4015.