title: 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.
  
  
  CONCLUSIONS
  These results suggest that TLR/MyD88/NF-kappaB signaling pathway plays a significant role in connecting inflammation and cancer invasion and progression.
authors.affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Mio
authors.initials: M
authors.lastname: Ikebe
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kitaura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Haruo
authors.initials: H
authors.lastname: Tanaka
authors.forename: Akio
authors.initials: A
authors.lastname: Yamasaki
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Nagai
authors.forename: Junji
authors.initials: J
authors.lastname: Wada
authors.forename: Kosuke
authors.initials: K
authors.lastname: Yanai
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Koga
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sato
authors.forename: Makoto
authors.initials: M
authors.lastname: Kubo
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Hideya
authors.initials: H
authors.lastname: Onishi
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Katano
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D053594:Myeloid Differentiation Factor 88 / Q000032:analysis / Q000502:physiology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000032:analysis / Q000502:physiology*
chemical_list: D008070:Lipopolysaccharides; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4