Interleukin-6 increases vascular endothelial growth factor and angiogenesis in gastric carcinoma
Interleukin-6 increases vascular endothelial growth factor and angiogenesis in gastric carcinoma
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DOI：
10.1159/000077902
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发表时间：
2004-01-01
影响因子：
11
通讯作者：
Lin, JT
中科院分区：
文献类型：
--
作者：
Huang, SP;Wu, MS;Lin, JT
白细胞介素-6（IL-6）是一种与胃癌（GC）病情相关的促炎细胞因子。血管内皮生长因子（VEGF）是胃癌中一种有效的肿瘤血管生成因子。在这项研究中，我们试图阐明IL-6是否可以调节GC中的VEGF和血管生成。对54例手术切除的胃癌标本进行了IL-6、VEGF和肿瘤微血管的免疫组化检测，结果表明IL-6与VEGF表达和肿瘤微血管呈正相关。我们通过ELISA测定了四种GC细胞系中VEGF的表达，揭示了GC细胞可以随着IL-6刺激的剂量和持续时间的增加而产生显著量的VEGF。接下来，采用荧光素酶报告基因测定来确定通过IL-6驱动VEGF启动子的信号传导途径，这表明JAK/STAT途径参与VEGF基因表达的刺激。分别通过HUVEC研究和Matrigel plug测定来评价IL-6对体外和体内血管生成的影响。结果表明，IL-6能有效地促进HUVEC体外增殖和管腔形成，并促进Matrigel栓血管形成，主要是通过诱导GC中的VEGF。这项研究提供的证据表明，多功能细胞因子，IL-6，可能会诱导VEGF的表达，增加血管生成在胃癌的发生。版权所有（C）2004国家科学理事会，中华民国和S. Karger AG，巴塞尔。
Interleukin-6 (IL-6) is a proinflammatory cytokine associated with the disease status of gastric carcinoma ( GC). Vascular endothelial growth factor ( VEGF) is a potent tumor angiogenic factor in GC. In this study, we attempted to clarify whether IL-6 can regulate VEGF and angiogenesis in GC. GC samples from 54 surgical specimens were subjected to immunohistochemical examination of IL-6, VEGF, and tumor microvessels, and results showed that IL-6 was positively correlated with VEGF expression and tumor vasculature. We determined VEGF expression in four GC cell lines by ELISA, revealing that GC cells can produce significant amount of VEGF with increasing dose and duration of IL-6 stimulation. Next, a luciferase reporter gene assay was employed to determine the signaling pathway driving the VEGF promoter by IL-6, which showed that the JAK/STAT pathway is involved in the stimulation of VEGF gene expression. The effects of IL-6 on angiogenesis in vitro and in vivo were evaluated by HUVEC studies and the Matrigel plug assay, respectively. Results showed that IL-6 effectively promoted HUVEC proliferation and tube formation in vitro and Matrigel plug vascularization in vivo, primarily by inducing VEGF in GC. This study provides evidence that the multifunctional cytokine, IL-6, may induce VEGF expression which increases angiogenesis in gastric carcinogenesis. Copyright (C) 2004 National Science Council, ROC and S. Karger AG, Basel.