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Toll like receptor‐9 agonists stimulate prostate cancer invasion in vitro
Author(s) -
Ilvesaro Joanna M.,
Merrell Melinda A.,
Swain Telisha Millender,
Davidson Jennifer,
Zayzafoon Majd,
Harris Kevin W.,
Selander Katri S.
Publication year - 2007
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20562
Subject(s) - tlr9 , prostate cancer , toll like receptor 9 , cancer research , cancer cell , lncap , immunohistochemistry , cpg site , receptor , biology , cancer , medicine , immunology , dna methylation , gene expression , gene , biochemistry
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. Prostate 67: 774–781, 2007. © 2007 Wiley‐Liss, Inc.