Short DNA sequences and bacterial DNA induce esophageal,gastric, and colorectal cancer cell invasion |
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Authors: | Joonas H Kauppila Tuomo J Karttunen Juha Saarnio Pia Nyberg Tuula Salo David E Graves Katri S Selander |
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Institution: | 1. Department of Anatomy and Cell Biology, University of Oulu, , Oulu, Finland;2. Department of Pathology, University of Oulu, , Oulu, Finland;3. Department of Surgery, University of Oulu, , Oulu, Finland;4. Oulu University Hospital, , Oulu, Finland;5. Institute of Dentistry, University of Oulu, , Oulu, Finland;6. Department of Chemistry, University of Alabama at Birmingham, , Birmingham, AL, USA |
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Abstract: | Toll‐like receptor 9 (TLR9) recognizes both bacterial and self‐DNA and it is abundantly expressed in the gastrointestinal tract. In this study, we investigated the influences of both bacterial DNA and specific short DNA sequences on TLR9‐mediated gastrointestinal cancer cell invasion. We assessed the effect of various DNA ligands on cellular invasion and on TLR9 and matrix metalloproteinase expression of three gastrointestinal cancer cell lines. DNA‐ligands described in this study include CpG‐ODN M362, 9‐mer (hairpin), human telomeric sequence h‐Tel22 G‐quadruplex, and bacterial DNAs from Escherichia coli and Helicobacter pylori. All of the DNAs studied were demonstrated to induce invasion in the studied cells. The DNA‐induced invasion was inhibited with a broad‐spectrum MMP inhibitor and partly also with chloroquine suggesting that it could be mediated via MMP activation, endosomal signaling, and TLR9. Interestingly, H. pylori DNA was shown to induce a more pronounced invasion in a gastric cancer cell line than in the other cell lines. Our results suggest that bacterial DNA as well as deoxynucleotides having stable secondary structures (i.e. hairpins or G‐quadruplex structures) may serve as endogenous, invasion‐inducing TLR9‐ligands and promote local progression and metastasis of cancers in the alimentary tract. |
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Keywords: | Toll‐like receptor 9 matrix metalloproteinase
Helicobacter pylori
Escherichia coli G‐quadruplex |
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