Konishi Naomi, Miki Chikao, Yoshida Toshimichi, Tanaka Koji, Toiyama Yuji, Kusunoki Masato
Second Department of Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu, Japan.
Oncology. 2005;68(2-3):138-45. doi: 10.1159/000086768. Epub 2005 Jul 4.
Interleukin (IL)-1 is known to act as a tumor growth factor by inducing angiogenic factors. We examined the significance of IL-1beta and IL-1 receptor antagonist (RA) for inducing the expression of vascular endothelial growth factor (VEGF) in colorectal cancers.
We investigated the expression of VEGF induced by IL-1beta in five colon cancer cell lines and the possible involvement of IL-1 RA. We also measured the tissue concentrations of IL-1beta, IL-1 RA and VEGF by ELISA in 65 colorectal cancer patients.
IL-1beta 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-1beta-induced VEGF secretion by 87%. Our data from the clinically obtained specimens showed that the IL-1 RA/IL-1beta ratio is significantly lower in cancer tissue. Regarding the clinicopathological parameters, the IL-1 RA/IL-1beta ratio was significantly lower in patients with vessel involvement than in those without involvement, and IL-1 RA/IL-1beta ratio was negatively correlated with the VEGF protein level in colorectal tumors.
Our data suggest that IL-1beta induces VEGF expression and IL-1 RA acts as the competitive inhibitor, and that the IL-1 RA/IL-1beta ratio is significant for VEGF expression in the microenvironment of colorectal cancer tissue. We conclude that IL-1beta 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.
已知白细胞介素（IL）-1可通过诱导血管生成因子发挥肿瘤生长因子的作用。我们研究了IL-1β和IL-1受体拮抗剂（RA）在结直肠癌中诱导血管内皮生长因子（VEGF）表达的意义。
我们研究了IL-1β在五种结肠癌细胞系中诱导的VEGF表达以及IL-1 RA可能的参与情况。我们还通过酶联免疫吸附测定法（ELISA）测量了65例结直肠癌患者组织中IL-1β、IL-1 RA和VEGF的浓度。
IL-1β诱导Caco-2细胞分泌VEGF，分泌量增加了19倍。在SW480和WiDr细胞中也观察到VEGF分泌显著增加。IL-1 RA抑制IL-1β诱导的VEGF分泌达87%。我们从临床获取标本的数据显示，癌组织中IL-1 RA/IL-1β比值显著降低。关于临床病理参数，血管受累患者的IL-1 RA/IL-1β比值显著低于未受累患者，且IL-1 RA/IL-1β比值与结直肠癌组织中的VEGF蛋白水平呈负相关。
我们的数据表明，IL-1β诱导VEGF表达，IL-1 RA起竞争性抑制剂的作用，且IL-1 RA/IL-1β比值在结直肠癌组织微环境中对VEGF表达具有重要意义。我们得出结论，IL-1β在一定比例的结直肠癌患者中诱导VEGF分泌，且IL-1 RA是结直肠癌患者抗血管生成治疗的潜在治疗药物。
