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-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.
Ikebe
Mio
M
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kitaura
Yoshiki
Y
Nakamura
Masafumi
M
Tanaka
Haruo
H
Yamasaki
Akio
A
Nagai
Shuntaro
S
Wada
Junji
J
Yanai
Kosuke
K
Koga
Kenichiro
K
Sato
Norihiro
N
Kubo
Makoto
M
Tanaka
Masao
M
Onishi
Hideya
H
Katano
Mitsuo
M
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*
D008070:Lipopolysaccharides; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4