白细胞介素-6刺激胰腺癌细胞中Th2型细胞因子的分泌，并上调血管内皮生长因子和神经毡蛋白-1的表达。

IL-6 stimulates Th2 type cytokine secretion and upregulates VEGF and NRP-1 expression in pancreatic cancer cells.

作者信息

Feurino Louis W, Zhang Yuqing, Bharadwaj Uddalak, Zhang Rongxin, Li Fei, Fisher William E, Brunicardi F Charles, Chen Changyi, Yao Qizhi, Min L

机构信息

Molecular Surgeon Research Center, Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, Baylor College of Medidcine, Houston, Texas 77030, USA.

出版信息

Cancer Biol Ther. 2007 Jul;6(7):1096-100. doi: 10.4161/cbt.6.7.4328.

DOI:10.4161/cbt.6.7.4328

PMID:17568185

Abstract

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, VEGF165, 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 VEGF165, 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 develop ment 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.

摘要

背景

尽管白细胞介素-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充分阐明。在本研究中，我们检测了IL-6在胰腺癌细胞中的表达，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

通过实时逆转录聚合酶链反应（RT-PCR）测定IL-6、血管内皮生长因子165（VEGF165）、神经纤毛蛋白-1（NRP-1）和神经纤毛蛋白-2（NRP-2）的mRNA水平。使用生物芯片磷酸化蛋白检测法测定胰腺癌细胞中细胞外调节蛋白激酶2（ERK2）的磷酸化水平。用人胰腺癌细胞系中的生物芯片细胞因子检测法测定IL-6和其他细胞因子的表达。

结果

胰腺癌细胞系中IL-6的表达水平高于正常人胰腺导管上皮（HPDE）细胞。外源性IL-6增加了Panc-1、MIA PaCa-2和BxPC-3细胞中多种Th2型细胞因子的分泌。IL-6还上调了VEGF165和NRP-1的表达，并且IL-6和VEGF165均可被缺氧诱导。此外，IL-6激活了胰腺癌细胞中的ERK2信号通路。