Lipopolysaccharide (LPS) Increases the Invasive Ability of Pancreatic Cancer Cells Through the TLR4/MyD88 Signaling Pathway
Lipopolysaccharide (LPS) Increases the Invasive Ability of Pancreatic Cancer Cells Through the TLR4/MyD88 Signaling Pathway
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DOI：
10.1002/jso.21392
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发表时间：
2009-12-15
影响因子：
2.5
通讯作者：
Katano, Mitsuo
中科院分区：
文献类型：
--
作者：
Ikebe, Mio;Kitaura, Yoshiki;Katano, Mitsuo
背景资料：炎症在癌症进展中起着多方面的作用，而NF-κ B B是连接炎症与癌症进展的关键因素之一。我们已经表明，脂多糖（LPS）促进NF-κ B B在结肠癌细胞和胰腺癌细胞的激活。然而，目前还不清楚为什么炎症刺激可以诱导NF-κ B B激活的癌cells.Methods：我们使用两个人胰腺癌细胞，Panc-1和AsPC-1，作为靶细胞。LPS被用作炎症刺激物。为了证实TLR 4/NF-κ B信号通路的参与，我们使用了三种不同的NF-κ B抑制剂（PDTC、I κ B α突变体和NF-κ B诱饵ODN）和siRNA（针对TLR 4、MyD 88和MMP-9）。结果：LPS可增强胰腺癌细胞的侵袭能力，而阻断NF-κ B B通路可降低LPS依赖的胰腺癌细胞的侵袭能力。结论：TLR/MyD 88/NF-κ B B信号通路在炎症反应与肿瘤侵袭和发展之间起重要作用。《肿瘤外科杂志》2009;100：725-731。(C)2009威利-利斯公司
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.