Prevention of Liver Metastasis by Cell-binding Domain

Noboru Saito, Maki Mitsuhashi, Tatsuhiro Hayashi, Hitoshi Nagata, Shingo Kameoka, Kyoichi Hamano, Satoru Harumiya¹⁾, Daisaburo Fujimoto¹⁾

Department of Surgery II Tokyo Women's Medical College
Department of Applied Biological Science, Faculty of Agriculture,Tokyo University of Agriculture and Technology¹⁾

In order to determine the role of cell adhesion molecules in the process of cancer invasion and metastasis, we administered the cell-binding domain to a mouse liver metastasis model, and assessed the prevention of cancer metastasis resulting from inhibition of adhesive interaction with cancer cells. A liver metastasis model was created by injecting 1×10³ colon 26/TC-1 cells into the anterior mesenteric vein of CDF1 mice. The cell-binding domain was obtained by extracting and purifying fibronectin from human plasma, and partially purifying only the domain which includes RGD. A fibronectin-treated group, a fibronectin binding domain-treated group, and a control group were established. The animais were sacrificed four weeks later, and the metastatic liver nodules were counted. The results showed that metastasis was more advanced in the fibronectin group than in the control group, and about 50% inhibition was observed in the fibronectin binding domain-treated group (10 µ of fibronection per m1). These findings suggest that, as a metastasis-inhibiting substance, the binding domain may become an effective means of anti-adhesion therapy by competing with native adhesion molecules on the cancer cell surface during the metastatic process, and blocking adhesion.

Key words
cell-binding domain, prevention of liver metastasis, fibronectin

Reprint requests
Noboru Saito Department of Surgery II, Tokyo Women's Medical College
8-1 Kawada-chou, Shinjyuku-ku, Tokyo, 162 JAPAN

Accepted
November 15, 1995

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