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Association of the multiple cell binding domains in fibronectin and cancer metastasis

Association of the multiple cell binding domains in fibronectin and cancer metastasis
纤连蛋白与癌症转移中多个细胞结合域的关联
批准号:
01570729
负责人:
KUBOMURA Shigeo
金额:
$1.41万
依托单位国家:
日本
项目类别:
Grant-in-Aid for General Scientific Research (C)
财政年份:
1989
资助国家:
日本
项目状态:
已结题
起止时间:
1989 至 1991

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中文摘要
翻译
据说,当癌细胞通过循环系统转移时,它们通过纤维连接蛋白或其他细胞外基质蛋白中的细胞结合域附着并渗透到靶器官。Gly-Arg-Gly-AspSer(Gly-Arg-Gly-AspSer,Gly-Arg-Gly-AspSer,在体外实验中,我们详细研究了人肝癌细胞系和大鼠肝癌细胞系。在细胞黏附和铺展抑制实验中,当GRGDS加入到培养液中时,这些细胞在涂有纤维连接蛋白的孔板上的黏附和铺展得到了较好的抑制。在这些细胞系中,抑制作用呈剂量依赖关系。在活体实验中,我们使用了雄性,冬雨大鼠。将大鼠肝癌细胞静脉注射到大鼠尾静脉。3周后,对照组大鼠肺内已形成转移的肝癌细胞集落。然而,静脉注射GRGDS的大鼠,肺内没有形成转移集落。今后,我们将综合考虑血药浓度等因素,研究提高疗效的方法。
英文摘要
It is said that cancer cells adhere to and infiltrate into a target organ using cell binding domains in fibronectin or the other extracellular matrix protein when they metastasize through the circulatory system. The first cell binding domain in fibronectin, Gly-Arg-Gly-AspSer (GRGDS), has been reported to depress the malignant melanoma cells implanting on lungs in murine experiments.In this study we conducted cell adhesion and spreading inhibition experiments and migration experiments, and metastasis inhibition experiments with rats, to see if the cell binding domain peptides in fibronectin can inhibit the implantation in digestive system cancer cells or other cancer cells. For the in vitro experiments, we studied human hepatoma cell lines and a rat hepatoma cell line in details. In the cell adhesion and spreading inhibition experiments, when GRGDS was added to the culture solution, the adhesion and spreading of these cells on the wellplate coated with fibronectin are fairly inhibited. The inhibition was dose dependent in these cell lines. In vivo experiments, we used male, Donryu rats. The rat hepatoma cells were intravenously injected into the tail vein of rats. Three weeks later, the metastasized colonies of hepatoma cells had been formed in the lungs of control rats. However, with the rats injected intravenously of GRGDS, no metastasized colony was formed in the lungs. In the future, we would like to study the methods to enhance the effect, taking blood concentration and other factors into consideration.
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