Clinical & Experimental Metastasis

, Volume 20, Issue 5, pp 431–435

Reduced angiogenesis in peritoneal dissemination of gastric cancer through gelatinase inhibition

  • Norihito Wada
  • Yoshihide Otani
  • Tetsuro Kubota
  • Masaru Kimata
  • Akiko Minagawa
  • Nobunari Yoshimizu
  • Kaori Kameyama
  • Yoshiro Saikawa
  • Masashi Yoshida
  • Toshiharu Furukawa
  • Masato Fujii
  • Koichiro Kumai
  • Yasunori Okada
  • Masaki Kitajima
Article

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 zymography gastric neoplasm marimastat matrix metalloproteinase inhibitor microvascular density peritoneal metastasis TMK-1 

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Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Norihito Wada
    • 1
    • 2
  • Yoshihide Otani
    • 1
  • Tetsuro Kubota
    • 1
  • Masaru Kimata
    • 1
  • Akiko Minagawa
    • 1
  • Nobunari Yoshimizu
    • 1
  • Kaori Kameyama
    • 3
  • Yoshiro Saikawa
    • 1
  • Masashi Yoshida
    • 1
  • Toshiharu Furukawa
    • 1
  • Masato Fujii
    • 4
  • Koichiro Kumai
    • 5
  • Yasunori Okada
    • 3
  • Masaki Kitajima
    • 1
  1. 1.Department of Surgery, School of MedicineKeio UniversityTokyoJapan
  2. 2.Department of SurgeryNational Tokyo Medical CenterTokyoJapan
  3. 3.Department of Pathology, School of MedicineKeio UniversityTokyoJapan
  4. 4.Department of Otolaryngology, School of MedicineKeio UniversityTokyoJapan
  5. 5.Center for Diagnostic and Therapeutic EndoscopyKeio University HospitalTokyoJapan

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