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Published on: October 24, 2019
Toll like receptor-9 agonists stimulate prostate cancer invasion in vitro
Joanna M Ilvesaro1, Melinda A Merrell, Telisha Millender Swain
1Department 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.
Insights
Toll-like receptor 9 (TLR9) in prostate cancer cells drives invasion via matrix metalloproteinase-13 (MMP-13), suggesting infections may promote cancer progression. This TLR9-mediated invasion was blocked by chloroquine and anti-MMP-13 antibodies.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Toll-like receptor 9 (TLR9) recognizes microbial DNA and is expressed in various cancer cells.
- Previous research demonstrated TLR9 agonistic CpG-oligonucleotides (CpG-ODNs) induce matrix metalloproteinase-13 (MMP-13)-mediated invasion in breast cancer cells.
Purpose of the Study:
- To investigate TLR9 expression and function in human prostate cancer (CaP) cells.
- To determine if TLR9 activation influences CaP cell invasion and MMP-13 activity.
Main Methods:
- TLR9 expression was assessed using Western blotting and immunohistochemistry.
- Cell invasion was evaluated via Matrigel assays, and MMP-13 activity was measured using ELISA.
- The effect of CpG-ODNs, bacterial DNA, chloroquine, and anti-MMP-13 antibodies on CaP cells was examined.
Main Results:
- Human CaP cell lines and clinical samples displayed variable TLR9 expression levels.
- Treatment with CpG-ODNs or bacterial DNA enhanced invasion in TLR9-expressing CaP cells, an effect inhibited by chloroquine.
- CpG-ODN stimulation increased MMP-13 activity, and blocking MMP-13 prevented CpG-ODN-induced invasion. Estradiol upregulated TLR9 in LnCaP cells.
Conclusions:
- TLR9 activation promotes invasion in human prostate cancer cells.
- MMP-13 plays a critical role in TLR9-mediated CaP cell invasion.
- TLR9-mediated invasion represents a potential mechanism linking infections to prostate cancer development.
