山梨医科大学雑誌　第11巻3号　037-047(1996)

Competitive Inhibition of Pulmonary Metastasis of Hamster Osteosarcoma by Peptides Containing the Core Sequence of Cell-Adhesive Mofecules

Takuzo NAKAGAWA and Noriya AKAMATSU

Abstract: Tumor invasion and metastasis may occur due to altered mechanisms of adhesion of cells to the extracellular matrix. The RGD sequence (Arg-Gly-Asp) commonly exists in some adhesion-related mofecules including fibronectin, vitronectin, fibrinogen and von Willebrand factor. It is believed that synthetic peptides containing the RGD core sequence are able to inhibit the formation of tumor colonies in the lungs. To control pulmonary metastases, the author investigated the antimetastatic activity of the RGD core sequence in the cell-binding fragment of fibronectin in the metastatic process of hamster osteosarcoma. Primary and metastatic tumor cells from hamster osteosarcoma were analyzed by cytofluorometry to investigate the populations of fibronectin receptors on the surface of each cell type. Inhibitors containing the characteristic sequence in fibronectin reduced metastatic colonization in the lung lesions. Fibronectin receptors on the cells from lung metastatic lesions increased compared to those from primary lesions. These results indicate that the mechanism of metastasis is related to the interaction between fibronectin and the fibronectin receptor. It also suggests that inhibitors which contain the RGD core sequence decrease pulmonary metastatic colonization through by interfering with the cellular adhesive process.

Key words: Osteosarcoma, Fibronectin receptor, Extracellular matrix, Pulmonary metastasis, Synthetic peptide




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