Lipopolysaccharide (LPS) Increases the Invasive Ability of Pancreatic Cancer Cells Through the TLR4/MyD88 Signaling Pathway

Background: Inflammation plays a multifaceted role in cancer progression, and NF-kappa B is one of the key factors connecting inflammation with cancer progression. We have shown that lipopolysaccharide (LPS) promotes NF-kappa B activation in colon cancer cells and pancreatic cancer cells. However, it is unclear why inflammatory stimuli can induce NF-kappa B 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-kappa B signaling pathway, we used three different NF-kappa B inhibitors (PDTC, I kappa B alpha mutant, and NF-kappa B 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-kappa B pathway decreased the LPS-dependent increased invasive ability. Blockade of TLR4 or MyD88 by siRNA also decreased the I-PS-dependent increased invasive ability. Conclusion: These results suggest that TLR/MyD88/NF-kappa B signaling pathway plays a significant role in connecting inflammation and cancer invasion and progression. J. Surg. Oncol. 2009;100:725-731. (C) 2009 Wiley-Liss, Inc.