IL-6 stimulates Th2 type cytokine secretion and upregulates VEGF and NRP-1 expression in pancreatic cancer cells
IL-6 stimulates Th2 type cytokine secretion and upregulates VEGF and NRP-1 expression in pancreatic cancer cells
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DOI：
10.4161/cbt.6.7.4328
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发表时间：
2007-07-01
影响因子：
3.6
通讯作者：
Li, Min
中科院分区：
文献类型：
--
作者：
Feurino, Louis W.;Zhang, Yuqing;Li, Min
背景：尽管白介素 6 (IL-6) 的上调与许多实体瘤相关，但其在胰腺癌中的作用尚未得到很好的阐明。在本研究中，我们检测了胰腺癌细胞中IL-6的表达，并确定了外源性IL-6对人胰腺癌细胞中细胞因子分泌、基因表达和信号传导的影响。方法：通过实时RT PCR测定IL-6、VEGF（165）、neuropilin-1（NRP-1）和neuropilin-2（NRP-2）的mRNA水平。使用 Bio-Plex 磷蛋白测定法测定胰腺癌细胞中 ERK2 的磷酸化。采用Bio-Plex细胞因子测定法测定人胰腺癌细胞系中IL-6和其他细胞因子的表达。结果：胰腺癌细胞系比正常人胰腺导管上皮（HPDE）细胞表达更高水平的IL-6。外源性IL-6增加Panc-1、MIA PaCa-2和BxPC-3细胞中多种Th2型细胞因子的分泌。 IL-6还上调VEGF(165)和NRP-1的表达，并且IL-6和VEGF165均可被缺氧诱导。此外，IL-6还激活胰腺癌细胞中的ERK2信号通路。结论：IL-6可能通过提供Th2型细胞因子环境、上调细胞增殖和血管生成相关基因，参与促进人类胰腺癌的发生发展。靶向 IL-6 可能是胰腺癌的有效治疗方法。
Background: Although upregulation of interleukin-6 (IL-6) is associated with many solid tumors, its role in pancreatic cancer has not been well elucidated. In this study, we examined the expression of IL-6 in pancreatic cancer cells, and determined the effect of exogenous IL-6 on cytokine secretion, gene expression and signaling in human pancreatic cancer cells.Methods: The mRNA levels of IL-6, VEGF(165), neuropilin-1 (NRP-1) and neuropilin-2 (NRP-2) were determined by real-time RT PCR. Phosphorylation of ERK2 in pancreatic cancer cells was determined by using Bio-Plex phosphoprotein assay. The expression of IL-6 and other cytokines in human pancreatic cancer cell lines was determined with Bio-Plex cytokine assay.Results: Pancreatic cancer cell lines expressed higher levels of IL-6 than normal human pancreatic ductal epithelium (HPDE) cells. Exogenous IL-6 increased the secretion of multiple Th2 type of cytokines in Panc-1, MIA PaCa-2 and BxPC-3 cells. IL-6 also upregulated the expression of VEGF(165), and NRP-1, and both IL-6 and VEGF165 were inducible by hypoxia. In addition, IL-6 activated ERK2 signaling pathways in pancreatic cancer cells.Conclusions: IL-6 may be involved in promoting human pancreatic cancer development by furnishing Th2 type of cytokine environment and upregulating cell proliferation and angiogenesis related genes. Targeting IL-6 might be an effective treatment for pancreatic cancer.