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

据认为，当癌细胞通过循环系统转移时，癌细胞利用纤连蛋白或其他细胞外基质蛋白中的细胞结合结构域粘附并浸润到靶器官中。纤维连接蛋白的第一个细胞结合区Gly-Arg-Gly-AspSer（GRGDS）在小鼠肺移植实验中对恶性黑色素瘤细胞有抑制作用，本研究采用大鼠进行了细胞粘附扩散抑制实验、细胞迁移实验和转移抑制实验。观察纤连蛋白中的细胞结合域肽是否能抑制消化系统癌细胞或其他癌细胞的着床。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。在细胞粘附和铺展抑制实验中，当GRGDS加入培养液中时，这些细胞在纤连蛋白包被的孔板上的粘附和铺展受到相当程度的抑制。在这些细胞系中的抑制是剂量依赖性的。在体内实验中，我们使用了雄性东柳大鼠。将大鼠肝癌细胞经尾静脉注射到大鼠体内。三周后，对照组大鼠肺内已形成肝癌细胞的转移集落。然而，静脉注射GRGDS的大鼠，在肺中没有形成转移的集落。今后，我们将考虑血药浓度等因素，研究提高效果的方法。

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.