Interaction Between Pancreatic Cancer Cells and Tumor-Associated Macrophages Promotes the Invasion of Pancreatic Cancer Cells and the Differentiation and Migration of Macrophages
Interaction Between Pancreatic Cancer Cells and Tumor-Associated Macrophages Promotes the Invasion of Pancreatic Cancer Cells and the Differentiation and Migration of Macrophages
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DOI：
10.1002/iub.1336
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发表时间：
2014-12-01
期刊：
影响因子：
4.6
通讯作者：
Song, Shaowei
中科院分区：
文献类型：
--
作者：
Meng, Fanbin;Li, Changling;Song, Shaowei
在这项研究中，胰腺癌细胞与巨噬细胞的相互作用对巨噬细胞的分化和功能以及胰腺癌细胞的体外行为的影响进行了评估。免疫组化法检测22例胰腺癌组织中免疫活性细胞相关标志物的表达。通过transwell法测定胰腺癌细胞（PANC-1和BxPC-3）对人U937单核细胞分化和迁移的影响以及U937衍生的巨噬细胞对PANC-1和BxPC-3的增殖和侵袭的影响。通过实时定量聚合酶链反应分析了在transwell系统中共培养后对U937衍生的巨噬细胞或胰腺癌细胞行为的潜在影响。巨噬细胞相关的CD 68和CD 163在胰腺癌组织中呈高水平表达。胰腺癌细胞促进了U937细胞的分化和U937衍生的巨噬细胞的迁移，但降低了巨噬细胞极化相关基因白细胞介素（IL）-10，IL-12 p40，诱导型一氧化氮合酶（iNOS）和CD 163的mRNA转录，特别是iNOS。此外，U937来源的M2巨噬细胞抑制胰腺癌细胞的增殖，但促进其侵袭。胰腺癌细胞与U937衍生的巨噬细胞共培养上调与胰腺癌的上皮-间质转化过程、血管生成和干性相关的基因的mRNA表达，但下调胰腺癌细胞中E-钙粘蛋白的表达。胰腺癌细胞和肿瘤相关巨噬细胞之间的相互作用可能在胰腺癌的进展中起关键作用。(c)2014 IUBMB Life，66（12）：835-846，2014
In this study, the impact of pancreatic cancer cell interaction with macrophages on the differentiation and function of macrophages and the behaviors of pancreatic cancer cells in vitro is evaluated. The expression of immunocompetent cell-associated markers in 22 pancreatic cancer specimens was characterized by immunohistochemistry. The impact of pancreatic cancer cells (PANC-1 and BxPC-3) on the differentiation and migration of human U937 monocytes and the effect of U937-derived macrophages on the proliferation and invasion of PANC-1 and BxPC-3 were determined by transwell assays. The potential effect on U937-derived macrophages or on the behaviors of pancreatic cancer cells following coculture in a transwell system was analyzed by quantitative real-time polymerase chain reaction. The high levels of macrophage-related CD68 and CD163 expression were detected in the pancreatic cancer specimens. Pancreatic cancer cells promoted the differentiation of U937 cells and migration of U937-derived macrophages, but decreased the mRNA transcripts of macrophage polarization-related genes of interleukin (IL)-10, IL-12p40, inducible nitric oxide synthase (iNOS), and CD163, particularly for iNOS. Furthermore, U937-derived M2 macrophages inhibited the proliferation of pancreatic cancer cells, but promoted their invasion. Coculture of pancreatic cancer cells with U937-derived macrophages upregulated the mRNA expression of genes associated with the epithelial-mesenchymal transition process, angiogenesis, and stemness of pancreatic cancer, but downregulated the expression of E-cadherin in pancreatic cancer cells. The interaction between pancreatic cancer cells and tumor-associated macrophages may play a pivotal role in the progression of pancreatic cancer. (c) 2014 IUBMB Life, 66(12):835-846, 2014