International Journal of Clinical Oncology

, Volume 6, Issue 5, pp 215–220 | Cite as

Inhibition of hepatic metastasis in mice treated with cell-binding domain of human fibronectin and angiogenesis inhibitor TNP-470

  • N. Saito
  • M. Mitsuhashi
  • T. Hayashi
  • C. Narumo
  • H. Nagata
  • K. Soyama
  • S. Kameoka
  • S. Harumiya
  • D. Fujimoto
ORIGINAL ARTICLE

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.

Key words Metastasis Cell-binding domain Fibronectin TNP-470 Angiogenesis Colon cancer 

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Copyright information

© The Japan Society of Clinical Oncology 2001

Authors and Affiliations

  • N. Saito
    • 1
  • M. Mitsuhashi
    • 1
  • T. Hayashi
    • 1
  • C. Narumo
    • 1
  • H. Nagata
    • 1
  • K. Soyama
    • 1
  • S. Kameoka
    • 1
  • S. Harumiya
    • 2
  • D. Fujimoto
    • 3
  1. 1.Department of Surgery II, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan Tel. +81-3-3353-8111 ext. 39251; Fax +81-3-5269-7334 e-mail: nobosaito@surg2.twmu.ac.jpJP
  2. 2.Cell Signaling, Graduate School, Tokyo Medical and Dental University, Tokyo, JapanJP
  3. 3.Department of Applied Biological Science, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, JapanJP

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