Department of General Surgery, Pancreatic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
IUBMB Life. 2014 Dec;66(12):835-46. doi: 10.1002/iub.1336. Epub 2014 Dec 30.
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.
在这项研究中，评估了胰腺癌细胞与巨噬细胞相互作用对巨噬细胞分化和功能的影响，以及胰腺癌细胞在体外的行为。通过免疫组织化学方法对 22 个胰腺癌细胞标本中免疫活性细胞相关标志物的表达进行了特征描述。通过 Transwell 测定法测定了胰腺癌细胞（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 增殖和侵袭的影响。通过定量实时聚合酶链反应分析了在 Transwell 系统中共培养对 U937 衍生的巨噬细胞或对胰腺癌细胞行为的潜在影响。在胰腺癌细胞标本中检测到高水平的巨噬细胞相关 CD68 和 CD163 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，但下调了巨噬细胞极化相关基因白细胞介素 (IL)-10、IL-12p40、诱导型一氧化氮合酶 (iNOS) 和 CD163 的 mRNA 转录物，特别是 iNOS。此外，U937 衍生的 M2 巨噬细胞抑制了胰腺癌细胞的增殖，但促进了其侵袭。胰腺癌细胞与 U937 衍生的巨噬细胞共培养上调了与胰腺癌细胞上皮-间充质转化过程、血管生成和干性相关的基因的 mRNA 表达，但下调了胰腺癌细胞中 E-钙黏蛋白的表达。胰腺癌细胞与肿瘤相关巨噬细胞的相互作用可能在胰腺癌的进展中发挥关键作用。
