Secretion of vascular endothelial growth factor from undifferentiated human thyroid carcinoma cell line (ACT-1)

未分化人甲状腺癌细胞系（ACT-1）分泌血管内皮生长因子

• 批准号: 10671118
• 负责人: MIKI Hitoshi
• 金额: $ 2.05万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671118/
• 关键词: thyroid anaplastic carcinoma; VEGF; metastasis; undifferentiated carcinoma; 血管内皮細胞増殖因子; 血管新生

Proliferation and metastasis of undifferentiated human thyroid carcinoma cell line (ACT-1) was studied. The doubling time of ACT-1 was 48 hours. Transplantation of ACT-1 (2.5 x 10ィイD15ィエD1 cells) into subcutaneous tissues of severe combined immunodeficient (SCID) mice resulted in growing tumor, and pulmonary metastasis occurred three months after transplantation. Moreover, 3.0 x 10ィイD15ィエD1 cells of ACT-1 formed lung nodules three months after injection into the tail vein of SCID mice.ACT-1 cells secreted IL-6, IL-8, M-CSF, GM-CSF and vascular endothelial growth factor (VEGF) in high concentration into culture medium. Expression of VEGF mRNA in ACT-1 was confirmed by RT-PCR. Expression of VEGF protein in surgically resected tissue from the patient from whom ACT-1 was derived was also confirmed by immunohistochemical method.The effect of IL-6 and IL-8 on VEGF secretion from ACT-1 was studied. IL-8 did not make any influence on secretion of VEGF. However, IL-6 (100 ng/ml) stimulated secretion of VEGF from ACT-1, and this effect of IL-6 on VEGF secretion was neutralized by anti IL-6 antibody. Therefore, IL-6 produced by ACT-1 itself seems to stimulate the secretion from ACT-1 of VEGF, which develops the host vessels to support growth of carcinoma.

对未分化的人甲状腺癌细胞株(ACT-1)进行了增殖和转移研究。ACT-1的倍增时间为48小时。将ACT1(2.5×10ィイD15ィエD1细胞)移植到严重联合免疫缺陷小鼠的皮下组织中，3个月后肿瘤生长，并出现肺转移。3个月后经尾静脉注射ACT-1的ACT-1细胞形成肺结节，ACT-1细胞分泌高浓度的IL-6、IL-8、M-ィイ、GM-CSF和血管内皮生长因子ィエ。逆转录聚合酶链式反应(RT-PCR)证实ACT-1细胞中有VEGFmRNA的表达。免疫组织化学方法检测ACT-1来源的手术切除组织中血管内皮生长因子的表达，研究IL-6和IL-8对ACT-1分泌血管内皮生长因子的影响。IL-8对血管内皮生长因子的分泌无影响。IL-6(100 ng/ml)刺激ACT-1分泌血管内皮生长因子，这种作用可被抗IL-6抗体中和。因此，ACT-1产生的IL-6本身似乎可以刺激ACT-1分泌血管内皮生长因子，从而形成支持肿瘤生长的宿主血管。