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

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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.