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

Abstract

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.

• Authors: Mio Ikebe, Yoshiki Kitaura, Masafumi Nakamura, Haruo Tanaka, Akio Yamasaki, Shuntaro Nagai, Junji Wada, Kosuke Yanai, Kenichiro Koga, Norihiro Sato, Makoto Kubo, Masao Tanaka, Hideya Onishi, Mitsuo Katano
• Journal: Journal of surgical oncology (J Surg Oncol) Vol. 100 Issue 8 Pg. 725-31 (Dec 15 2009) ISSN: 1096-9098 [Electronic] United States
• PMID: 19722233 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Wiley-Liss, Inc.

Chemical References

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

Topics

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