Toll like receptor-9 agonists stimulate prostate cancer invasion in vitro.
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.
Ilvesaro
Joanna M
JM
Department of Medicine, Division of Hematology-Oncology, University of Alabama at Birmingham, Birmingham, Alabama 35294-3300, USA.
Merrell
Melinda A
MA
Swain
Telisha Millender
TM
Davidson
Jennifer
J
Zayzafoon
Majd
M
Harris
Kevin W
KW
Selander
Katri S
KS
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*
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