Nasopharyngeal carcinoma (NPC) is highly prevalent in Southeast Asia. It is characterized by its strong etiologic association with Epstein-Barr virus (EBV) infection, and its highly invasive and metastatic nature. The underlying mechanism for its high metastatic potential is poorly understood. To enable spreading (metastasis), cancer cells need to detach from their primary sites and survive in the absence of extracellular matrix (ECM). Anoikis is a programmed cell death resulted from the loss-of-contact with ECM. Proliferation/survival of normal epithelial cells is guarded by anoikis to ensure its survival in a matrix-dependent status. However, many cancer cells acquire anoikis resistance for their survival in the detached status for metastasis. The neurotrophin receptor TrkB and its ligand, brain-derived neurotrophic factor (BDNF), are key players in anoikis suppression in cancer. BDNF/TrkB overexpression, which is often associated with poor prognosis in many malignancies, has been reported in NPC. Here, we investigated the possible involvement of BDNF/TrkB signaling in NPC tumorigenesis. BDNF mRNA expression was detected in 7/11 (~64%) NPC patient biopsies. TrkB and BDNF were expressed in a representative NPC cell line, HONE-1-EBV. Several NPC cell lines, when grown on neutrally charged plates, were able to proliferate in a detached status. For HONE-1-EBV, BDNF (50 ng/ml) enhanced cellular proliferation in suspension. This effect was blocked by the pan-Trk inhibitor, K252a (300nM). BDNF also induced HONE-1-EBV cellular migration through the transwell chamber in a dose-dependent manner. Therefore, BDNF/TrkB signaling enhances the migration and survival of the anoikis resistant NPC cells, which may contribute to NPC invasiveness.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2169.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO