Short DNA sequences and bacterial DNA induce esophageal, gastric, and colorectal cancer cell invasion

APMIS. 2013 Jun;121(6):511-22. doi: 10.1111/apm.12016. Epub 2012 Oct 22.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Caco-2 Cells
  • Chloroquine / pharmacology
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • DNA, Bacterial / adverse effects*
  • Dipeptides / pharmacology
  • Enzyme Activation
  • Escherichia coli / genetics
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Helicobacter pylori / genetics
  • Humans
  • Ligands
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • Neoplasm Invasiveness / prevention & control
  • Oligodeoxyribonucleotides / pharmacology*
  • Protein Structure, Secondary
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Toll-Like Receptor 9 / antagonists & inhibitors*
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / metabolism


  • CPG-oligonucleotide
  • DNA, Bacterial
  • Dipeptides
  • Ligands
  • Matrix Metalloproteinase Inhibitors
  • N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide
  • Oligodeoxyribonucleotides
  • RNA, Messenger
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • Chloroquine
  • MMP9 protein, human
  • Matrix Metalloproteinase 9