Inhibition of cervical lymph node metastasis by marimastat (BB-2516) in an orthotopic oral squamous cell carcinoma implantation model.

Abstract

Activation of matrix metalloproteinase-2 (MMP-2) is a common event in head and neck squamous cell carcinoma. An OSC-19 cell line, derived from human oral squamous cell carcinoma and known to metastasize to cervical lymph nodes, was implanted into the lingual margin of mice. The effect of marimastat (BB-2516), a broad MMP inhibitor, on the suppression of regional cervical lymph node metastasis was evaluated with an orthotopic implantation nude mice model. Marimastat was given immediately after OSC-19 implantation and continuously administered by an osmotic pump. The mice were divided into three groups by marimastat dose; Group A; 0 mg/kg/day, Group B; 30 mg/kg/day, and Group C; 150 mg/kg/day. Twenty-one days after implantation, primary oral tumors and cervical lymph nodes were resected. Cervical lymph node status was microscopically examined. Activation of MMP-2 in primary oral tumor was examined by gelatin zymography. Both cervical lymph node metastasis and activation of MMP-2 were significantly suppressed in Group C (P < 0.05). Moreover, the Group C mice had a significantly better survival than group A (P = 0.0026). There was a significant difference between Group A and Group C in terms of proliferation of tumor cells by proliferating cell nuclear antigen immunostaining (P = 0.0120). These results suggest a positive role for marimastat in the inhibition of MMP-2 activation and prevention of cervical lymph node metastasis in oral squamous cell carcinoma (OSCC). Improvement of survival in patients with OSCC could be expected using adjuvant therapy with marimastat.

• Authors: Ken-ichi Maekawa, Hiroshi Sato, Mitsuru Furukawa, Tomokazu Yoshizaki
• Journal: Clinical & experimental metastasis (Clin Exp Metastasis) Vol. 19 Issue 6 Pg. 513-8 ( 2002) ISSN: 0262-0898 [Print] Netherlands
• PMID: 12405288 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Enzyme Inhibitors
• Hydroxamic Acids
• Matrix Metalloproteinase Inhibitors
• marimastat
• Matrix Metalloproteinase 2

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Squamous Cell (drug therapy, pathology)
• Cell Division (drug effects)
• Enzyme Inhibitors (therapeutic use)
• Humans
• Hydroxamic Acids (therapeutic use)
• Lymphatic Metastasis (prevention & control)
• Male
• Matrix Metalloproteinase 2 (analysis)
• Matrix Metalloproteinase Inhibitors
• Mice
• Mice, Nude
• Mouth Neoplasms (drug therapy, pathology)
• Time Factors
• Transplantation, Heterologous