Lipopolysaccharide (LPS) increases the invasive ability of pancreatic cancer cells through the TLR4/MyD88 signaling pathway

J Surg Oncol. 2009 Dec 15;100(8):725-31. doi: 10.1002/jso.21392.


Background: Inflammation plays a multifaceted role in cancer progression, and NF-kappaB is one of the key factors connecting inflammation with cancer progression. We have shown that lipopolysaccharide (LPS) promotes NF-kappaB activation in colon cancer cells and pancreatic cancer cells. However, it is unclear why inflammatory stimuli can induce NF-kappaB activation in cancer cells.

Methods: We used two human pancreatic cancer cells, Panc-1 and AsPC-1, as target cells. LPS was used as an inflammatory stimulus. To confirm the participation of TLR4/NF-kappaB signaling pathway, we used three different NF-kappaB inhibitors (PDTC, IkappaBalpha mutant, and NF-kappaB decoy ODN) and siRNAs (against TLR4, MyD88, and MMP-9). Effect of LPS on pancreatic cancer cell invasive ability was determined by Matrigel invasion assay.

Results: LPS increased the invasive ability of pancreatic cancer cells, while blockade of NF-kappaB pathway decreased the LPS-dependent increased invasive ability. Blockade of TLR4 or MyD88 by siRNA also decreased the LPS-dependent increased invasive ability.

Conclusion: These results suggest that TLR/MyD88/NF-kappaB signaling pathway plays a significant role in connecting inflammation and cancer invasion and progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Humans
  • Lipopolysaccharides / toxicity*
  • Myeloid Differentiation Factor 88 / analysis
  • Myeloid Differentiation Factor 88 / physiology*
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / pathology*
  • Signal Transduction / physiology*
  • Toll-Like Receptor 4 / analysis
  • Toll-Like Receptor 4 / physiology*


  • Lipopolysaccharides
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • TLR4 protein, human
  • Toll-Like Receptor 4