Abstract
Background. To prevent tumor metastasis, we administered the cell-binding domain of fibronectin, in combination with the angiogenesis inhibitor TNP-470, to mice with hepatic metastasis. We then assessed the prevention of tumor metastasis resulting from the inhibition of adhesive interactions and the inhibition of angiogenesis.
Methods. A hepatic 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 obtained from fibronectin included the Arg-Gly-Asp (RGD) sequence. A fibronectin-binding domain (FND)-treated group, an FND plus TNP-470 group, and a control group were established. The animals were killed 4 weeks after the injections of the treatment agents had been completed and the number of metastatic liver nodules was counted. In a simultaneous experiment with the same design, the mice were not killed at 4 weeks, and their survival was observed.
Results. The mean number of nodules in the FND plus TNP-470 group was significantly lower than that in the control group (P = 0.019337). The inhibition rate was 51% in the FND group, 60% in the FND 10 μg plus TNP-470 10 mg/kg group, and 64% in the FND 10 μg plus TNP-470 100 mg/kg group compared with the control group. Mice from the FND group that were not killed died after 6–8 weeks, but mice from the FND plus TNP-470 group died after 8–12 weeks.
Conclusion. The cell-binding domain of fibronectin may, potentially, be an effective form of antiadhesive therapy that competes with native adhesion molecules and blocks adhesion during the metastatic process. When the cell-binding domain of fibronectin is combined with TNP-470 to inhibit angiogenesis, more effective inhibition of metastatic tumor growth and prolongation of survival can be achieved than after treatment with the cell-binding domain alone.
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Received: December 19, 2000 / Accepted: August 10, 2001
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Saito, N., Mitsuhashi, M., Hayashi, T. et al. Inhibition of hepatic metastasis in mice treated with cell-binding domain of human fibronectin and angiogenesis inhibitor TNP-470. Int J Clin Oncol 6, 215–220 (2001). https://doi.org/10.1007/PL00012108
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DOI: https://doi.org/10.1007/PL00012108