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- Title
Short DNA sequences and bacterial DNA induce esophageal, gastric, and colorectal cancer cell invasion.
- Authors
Kauppila, Joonas H.; Karttunen, Tuomo J.; Saarnio, Juha; Nyberg, Pia; Salo, Tuula; Graves, David E.; Lehenkari, Petri P.; Selander, Katri S.
- 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.
- Subjects
ESOPHAGEAL cancer; STOMACH cancer; COLON cancer; NUCLEOTIDE sequence; BACTERIAL DNA; TOLL-like receptors; GASTROINTESTINAL system; CANCER cells
- Publication
APMIS, 2013, Vol 121, Issue 6, p511
- ISSN
0903-4641
- Publication type
Article
- DOI
10.1111/apm.12016