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  • Title: Toll like receptor-9 agonists stimulate prostate cancer invasion in vitro.
    Author: Ilvesaro JM, Merrell MA, Swain TM, Davidson J, Zayzafoon M, Harris KW, Selander KS.
    Journal: Prostate; 2007 May 15; 67(7):774-81. PubMed ID: 17373717.
    Abstract:
    BACKGROUND: Toll-like receptor 9 (TLR9) recognizes microbial DNA. In addition to immune cells, TLR9 expression has been detected in various cancer cells. We showed recently that TLR9 agonistic CpG-oligonucleotides (CpG-ODNs) induce matrix metalloproteinase-13 (MMP-13)-mediated invasion in TLR9-expressing (TLR9(+)) breast cancer cells. We investigated here TLR9 expression and function in human prostate cancer (CaP) cells. METHODS: TLR9 expression was detected with Western blotting and immunohistochemistry. Invasion was studied with Matrigel-assays. MMP-13 was assayed with ELISA. RESULTS: Human CaP cell lines and clinical samples exhibit various levels of TLR9 expression. Treatment of TLR9(+), but not TLR9(-) CaP cells with CpG-ODNs or bacterial DNA increased their invasion, which was inhibited with chloroquine. CpG-ODN-treatment also increased MMP-13 activity and neutralizing anti-MMP-13 antibody prevented CpG-ODN-induced invasion in TLR9(+) CaP cells. Estradiol up-regulated TLR9 expression in LnCaP cells. CONCLUSIONS: TLR9-mediated invasion may represent a novel mechanism through which infections promote prostate cancer.
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