title: Toll like receptor-9 agonists stimulate prostate cancer invasion in vitro.
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.
authors: Department of Medicine, Division of Hematology-Oncology, University of Alabama at Birmingham, Birmingham, Alabama 35294-3300, USA.
authors: Joanna M
authors: JM
authors: Ilvesaro
authors: Melinda A
authors: MA
authors: Merrell
authors: Telisha Millender
authors: TM
authors: Swain
authors: Jennifer
authors: J
authors: Davidson
authors: Majd
authors: M
authors: Zayzafoon
authors: Kevin W
authors: KW
authors: Harris
authors: Katri S
authors: KS
authors: Selander
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000962:Antimalarials / Q000494:pharmacology; D045744:Cell Line, Tumor; D002738:Chloroquine / Q000494:pharmacology; D004269:DNA, Bacterial / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D007239:Infections / Q000150:complications; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000502:physiology; D009361:Neoplasm Invasiveness; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D051217:Toll-Like Receptor 9 / Q000819:agonists* / Q000235:genetics / Q000502:physiology*
chemical_list: D000276:Adjuvants, Immunologic; D000962:Antimalarials; C408982:CPG-oligonucleotide; D004269:DNA, Bacterial; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D004958:Estradiol; D002738:Chloroquine; D053509:Matrix Metalloproteinase 13