Functional expression of TLR9 is associated to the metastatic potential of human lung cancer cell: functional active role of TLR9 on tumor metastasis.

CpG-oligonucleotides (CpG-ODN), which induce signaling through Toll-like receptor 9 (TLR9), are widely used as adjuvants in therapy against cancer. However, tumor cells express functional TLR9 were recently reported and the immune effect of CpG ODN on tumor cells remains unclear. Here we investigated the direct effects of CpG ODN on human tumor cell line 95D cells using flow cytometric analysis and Western blotting. We found strongly high expression of TLR9 in 95D cells. Stimulation of 95D cells with CpG ODN induced significantly elevated secretion of IL-1alpha and IL-8, as well as the expression of CXCR4, ICAM-1 and MMP-2. Furthermore, the invasion of 95D cells and TLR9 modifying 95C cells were significantly enhanced by stimulation of CpG ODN, which could be abrogated by inhibitory CpG ODN and chloroquine. These results suggest that functionally active TLR9 is expressed on human tumor cell lines, and may represent a novel insight on the role of TIL9 agonist used in tumor immunotherapy.