TLR3 activation inhibits nasopharyngeal carcinoma metastasis via down-regulation of chemokine receptor CXCR4

Abstract

Toll-like receptor 3 (TLR3), a receptor for viral double strain RNA (dsRNA), mediates anti-viral immune response by activating the innate immunity and cross-priming CD8(+) T cells. TLR3 agonists can directly trigger apoptosis in human cancer cells, and have been used as adjuvants to treat cancer patients with the aim of inducing an IFN-dependent immune response. In this study, we examined the effect of TLR3 activation on the metastasis of nasopharyngeal carcinoma (NPC). We found that NPC cells expressed TLR3 gene transcript and protein. TLR3 activation downregulated the expression of chemokine receptor CXCR4 in a dose-dependent manner, and inhibited cell migration in response to CXCR4 ligand stromal cell-derived factor-1alpha (SDF-1alpha) in chemotaxis assays. Furthermore, TLR3 activation significantly reduced the capacity of NPC cells to form metastasis in draining lymph nodes when injected in athymic mice. The anti-metastasis activity of endogenous human TLR3 expression in cancer cells reveals a novel aspect of the multiple-faced TLR biology, which may open new clinical prospects for using TLR3 agonists to control cancer metastasis in selected cancers.