The impact of acute inflammation on progression and metastasis in pancreatic cancer animal model

The impact of acute inflammation on progression and metastasis in pancreatic cancer animal model
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DOI:
10.1016/j.suronc.2017.11.008
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发表时间:
2018-03-01
影响因子:
2.3
通讯作者:
Chun, Young-Ok
Chun, Young-Ok
中科院分区:
医学4区
文献类型:
--
作者:
Ahn, Keun Soo;Hwang, Ji Yeon;Chun, Young-Ok

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背景:急性炎症对癌症的影响尚不清楚。因此,我们评估了急性炎症对癌症进展的影响,在动物模型中的形态学变化,以及分子features.Material和方法:小鼠胰腺导管腺癌细胞系(Panc-02)和酵母多糖分别用于诱导癌症和急性炎症,在C57/BL 6小鼠。在C组(n = 10)中,将2 × 107个Panc 02细胞注射到胰腺尾部。Z1组(n = 10)和Z2组(n = 10)在瘤细胞注射后,分别腹腔注射酵母多糖3 mg一次和两次。注射肿瘤细胞4周后处死所有小鼠。结果:Z2组炎症程度较其他两组严重。Z2组的肿瘤体积大于C组(P = 0.032),Z2组的肝转移明显多于C组和Z1组(P = 0.025)。共聚焦显微镜分析显示,Z2组肝脏和胰腺中Snail、EpCAM、Muc 1、NLRP 3和miR-155的表达显著高于其他两组。流式细胞术检测Z2组血标本中EpCAM和Muc 1的表达,而其他两组均未检测到。与C组和Z1组相比,Z2组E-Cadherin表达减弱,Vimentin、snail 1表达增强。结论:急性炎症伴发的恶性肿瘤通过上皮细胞向间质细胞转化(EMT)和循环肿瘤细胞(CTC)促进恶性肿瘤的进展。(C)2017爱思唯尔有限公司版权所有
Background: The impact of acute inflammation on cancer is unclear. Therefore, we evaluated the impact of acute inflammation on cancer progression in an animal model concerning morphological change as well as molecular features.Material and methods: Murine pancreas ductal adenocarcinoma cell line (Panc-02) and zymosan were used for the induction of cancer and acute inflammation respectively, in C57/BL6 mice. In the C group (n = 10), 2 x 10(7) Panc02 cells were injected into the tail of the pancreas. In the Z1 (n = 10) and Z2 (n = 10), 3 mg of zymosan was injected intraperitoneally once and twice respectively, after tumor cell injection. All of the mice were sacrificed 4 weeks after tumor cell injection.Results: The degree of inflammation was more severe in the Z2 group than in the other two groups. The tumor volume of the Z2 group was larger than that of the C group (P = 0.032) and the presence of liver metastasis was significantly more common in the Z2 group than in the C and Z1 groups (P = 0.025). Confocal microscopy analysis revealed significantly more expression of Snail, EpCAM, Muc1, NLRP3 and miR-155 in the liver and pancreas in the Z2 group than in the other two groups. EpCAM and Muc1 were detected in blood samples in the Z2 group by flow cytometry, but not in the other two groups. In the Z2, expression of E-Cadherin was weaker and vimentin, snail1 were stronger compared to the C and Z1 group in the PCR and western blot.Conclusion: Present results suggest that acute inflammation accompanied with cancer promotes cancer progression by the epithelial-to-mesenchymal transition (EMT) and circulating tumor cells (CTC) process. (C) 2017 Elsevier Ltd. All rights reserved.