title: 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.affiliation: Department of Otolaryngology, School of Medicine, Kanazawa University, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Maekawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Furukawa
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Yoshizaki
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D008207:Lymphatic Metastasis / Q000517:prevention & control*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000473:pathology*; D013997:Time Factors; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; C100342:marimastat; D020778:Matrix Metalloproteinase 2