Serveur d'exploration Chloroquine

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Toll like receptor‐9 agonists stimulate prostate cancer invasion in vitro

Identifieur interne : 001A90 ( Main/Exploration ); précédent : 001A89; suivant : 001A91

Toll like receptor‐9 agonists stimulate prostate cancer invasion in vitro

Auteurs : Joanna M. Ilvesaro [États-Unis] ; Melinda A. Merrell [États-Unis] ; Telisha Millender Swain [États-Unis] ; Jennifer Davidson [États-Unis] ; Majd Zayzafoon [États-Unis] ; Kevin W. Harris [États-Unis] ; Katri S. Selander [États-Unis]

Source :

RBID : ISTEX:97BE15C3CAAE90F9CCC7175ACC7239A5004403B4

English descriptors

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. Prostate 67: 774–781, 2007. © 2007 Wiley‐Liss, Inc.

Url:
DOI: 10.1002/pros.20562


Affiliations:


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<term>Chloroquine</term>
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<term>Ligand</term>
<term>Lncap</term>
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<term>Lower wells</term>
<term>Microbial</term>
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<term>Negative staining control</term>
<term>Neutralizing antibody</term>
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<term>Pca2b prostate cancer cells</term>
<term>Primary antibody</term>
<term>Prostate</term>
<term>Prostate cancer</term>
<term>Prostate cancer cells</term>
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<term>Prostate cancer progression</term>
<term>Prostate cancer risk</term>
<term>Prostate carcinogenesis</term>
<term>Prostate gland</term>
<term>Receptor</term>
<term>Receptors tlr4</term>
<term>Steroid biochem</term>
<term>Stromal cells</term>
<term>Subcellular localization</term>
<term>Synthetic inhibitors</term>
<term>Testosterone</term>
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<term>Tlr9 agonists</term>
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<div type="abstract" xml:lang="en">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.</div>
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