Interleukin-1 receptor antagonist inhibits the expression of vascular endothelial growth factor in colorectal carcinoma
Interleukin-1 receptor antagonist inhibits the expression of vascular endothelial growth factor in colorectal carcinoma
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DOI：
10.1159/000086768
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发表时间：
2005-01-01
期刊：
影响因子：
3.5
通讯作者：
Kusunoki, M
中科院分区：
文献类型：
--
作者：
Konishi, N;Miki, C;Kusunoki, M
目的：白细胞介素（IL）-1是一种肿瘤生长因子，通过诱导血管生成因子发挥作用。我们研究了IL-1 β和IL-1受体拮抗剂（RA）诱导大肠癌血管内皮生长因子（VEGF）表达的意义。方法：我们研究了IL-1 β诱导的5种结肠癌细胞系VEGF的表达以及IL-1 RA的可能参与。我们还用ELISA法测定了65例结直肠癌患者组织中IL-1 β、IL-1 RA和VEGF的浓度。结果：IL-1 β诱导Caco-2细胞VEGF分泌增加19倍。在SW 480和WiDr细胞中也观察到VEGF分泌的显著增加。IL-1 RA抑制IL-1 β诱导的VEGF分泌达87%。我们从临床获得的样本中获得的数据显示，IL-1 RA/IL-1 β比率在癌组织中显著较低。关于临床病理参数，IL-1 RA/IL-1 β比值在有血管受累的患者中显著低于无血管受累的患者，并且IL-1 RA/IL-1 β比值与结直肠肿瘤中VEGF蛋白水平呈负相关。结论：我们的数据表明，IL-1 β诱导VEGF的表达和IL-1 RA作为竞争性抑制剂，和IL-1 RA/IL-1 β的比例是显着的大肠癌组织的微环境中的VEGF表达。我们的结论是，IL-1 β诱导VEGF分泌在一定的人群中的结直肠癌患者，IL-1 RA是潜在的治疗剂，抗血管生成治疗结直肠癌患者。版权所有（C）2005 S. Karger AG，巴塞尔。
Objective: Interleukin (IL)-1 is known to act as a tumor growth factor by inducing angiogenic factors. We examined the significance of IL-1 beta and IL-1 receptor antagonist (RA) for inducing the expression of vascular endothelial growth factor (VEGF) in colorectal cancers. Methods: We investigated the expression of VEGF induced by IL-1 beta in five colon cancer cell lines and the possible involvement of IL-1 RA. We also measured the tissue concentrations of IL-1 beta, IL-1 RA and VEGF by ELISA in 65 colorectal cancer patients. Results: IL-1 beta induced VEGF secretion with a 19-fold increase in Caco-2 cells. A significant increase in VEGF secretion was also observed in SW480 and WiDr cells. IL-1 RA inhibited IL-1 beta-induced VEGF secretion by 87%. Our data from the clinically obtained specimens showed that the IL-1 RA/IL-1 beta ratio is significantly lower in cancer tissue. Regarding the clinicopathological parameters, the IL-1 RA/IL-1 beta ratio was significantly lower in patients with vessel involvement than in those without involvement, and IL-1 RA/IL-1 beta ratio was negatively correlated with the VEGF protein level in colorectal tumors. Conclusions: Our data suggest that IL-1 beta induces VEGF expression and IL-1RA acts as the competitive inhibitor, and that the IL-1RA/IL-1 beta ratio is significant for VEGF expression in the microenvironment of colorectal cancer tissue. We conclude that IL-1 beta induces VEGF secretion in a certain population of colorectal cancer patients, and that IL-1 RA is the potential therapeutic agent for antiangiogenic therapy in colorectal cancer patients. Copyright (C) 2005 S. Karger AG, Basel.