Prostate Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Prostate Cancer, including details on symptoms, genetics, screening, treatment, information.

Toll like receptor-9 agonists stimulate prostate cancer invasion in vitro.

Ilvesaro JM, Merrell MA, Swain TM, Davidson J, Zayzafoon M, Harris KW, Selander KS

Department of Medicine, Division of Hematology-Oncology, University of Alabama at Birmingham, Birmingham, Alabama 35294-3300, USA.

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.

Published 3 April 2007 in Prostate, 67(7): 774-81.
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