Clinical & Experimental Metastasis

, Volume 20, Issue 5, pp 431–435

Reduced angiogenesis in peritoneal dissemination of gastric cancer through gelatinase inhibition

Authors

  • Norihito Wada
    • Department of Surgery, School of MedicineKeio University
    • Department of SurgeryNational Tokyo Medical Center
    • Department of Surgery, School of MedicineKeio University
  • Tetsuro Kubota
    • Department of Surgery, School of MedicineKeio University
  • Masaru Kimata
    • Department of Surgery, School of MedicineKeio University
  • Akiko Minagawa
    • Department of Surgery, School of MedicineKeio University
  • Nobunari Yoshimizu
    • Department of Surgery, School of MedicineKeio University
  • Kaori Kameyama
    • Department of Pathology, School of MedicineKeio University
  • Yoshiro Saikawa
    • Department of Surgery, School of MedicineKeio University
  • Masashi Yoshida
    • Department of Surgery, School of MedicineKeio University
  • Toshiharu Furukawa
    • Department of Surgery, School of MedicineKeio University
  • Masato Fujii
    • Department of Otolaryngology, School of MedicineKeio University
  • Koichiro Kumai
    • Center for Diagnostic and Therapeutic EndoscopyKeio University Hospital
  • Yasunori Okada
    • Department of Pathology, School of MedicineKeio University
  • Masaki Kitajima
    • Department of Surgery, School of MedicineKeio University
Article

DOI: 10.1023/A:1025453500148

Cite this article as:
Wada, N., Otani, Y., Kubota, T. et al. Clin Exp Metastasis (2003) 20: 431. doi:10.1023/A:1025453500148

Abstract

Marimastat is a broad-spectrum matrix metalloproteinase (MMP) inhibitor that inhibits almost all major MMPs, key enzymes in gastric cancer invasion and metastasis. We investigated the ability of marimastat to inhibit tumor angiogenesis in the severe combined immuno-deficient (SCID) mouse/human gastric cancer model of peritoneal dissemination. A human stomach adenocarcinoma cell line, TMK-1, was injected intraperitoneally into SCID mice. On the 7th day after tumor inoculation, the administration of marimastat (27 mg/kg/day) was initiated and the treatment was continued for 2 weeks using subcutaneously-inoculating mini-osmotic pumps. On the 21st day, the mice were killed and the disseminated nodules were evaluated. Total weights, numbers, and the microvascular density of the disseminating nodules were significantly lower in mice treated with marimastat compared to the control group. Film in situ zymography demonstrated that net gelatinolytic activity in the tissues was weaker in treated-group nodules than in control-group nodules. Thus, our results suggested that marimastat inhibited peritoneal dissemination of human gastric cancer cells through inhibition of tumor angiogenesis, possibly involving the down-regulation of gelatinases, in SCID mice injected with human gastric cancer cells.

film in situ zymographygastric neoplasmmarimastatmatrix metalloproteinase inhibitormicrovascular densityperitoneal metastasisTMK-1
Download to read the full article text

Copyright information

© Kluwer Academic Publishers 2003