Inhibition of ameloblastoma invasion in vitro and in vivo by inhibitor of metalloproteinase-2 activity

• Published in: Journal of oral pathology & medicine 2009-10, Vol.38 (9), p.731-736
• Main Authors: Zhang, Bin, Zhang, Jin, Huang, Hong-Zhang, Chen, Wei-Liang, Tao, Qian, Zeng, Dong-Lin, Zhang, Lei-Tao, Xu, Jian-Hui
• Format: Article
• Language: English
• Subjects: ameloblastoma; Ameloblastoma - drug therapy; Ameloblastoma - enzymology; Animals; Biological and medical sciences; Dentistry; Facial bones, jaws, teeth, parodontium: diseases, semeiology; Humans; invasion; Jaw Neoplasms - drug therapy; Jaw Neoplasms - enzymology; Matrix Metalloproteinase 2 - physiology; Matrix Metalloproteinase Inhibitors; Medical sciences; metalloproteinase-2 activity; metalloproteinase-2 inhibitor; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Neoplasm Transplantation; Otorhinolaryngology. Stomatology; Tissue Inhibitor of Metalloproteinase-2 - pharmacology; Tissue Inhibitor of Metalloproteinase-2 - therapeutic use; Tumor Cells, Cultured; Tumors
• ISSN: 0904-2512; 1600-0714
• DOI: 10.1111/j.1600-0714.2009.00771.x

Background:  Ameloblastoma is an odontogenic benign tumor characterized by local invasiveness and most of its local recurrences clinically result from local invasion. This study used matrix metalloproteinase‐2 (MMP‐2) inhibitor I (MMP‐2I) to investigate the role played by MMP‐2 activity in the local invasiveness of ameloblastoma. Methods:  The cells and xenografts of ameloblastoma were treated with MMP‐2I and treatment group were compared with the control group. In vitro, the invasive activity of tumor cells was assayed in transwell cell culture chamber. Gelatinolytic activity of gelatinases and MMP‐2/tissue inhibitor of matrix metalloproteinase (TIMP‐2) protein expression was detected using gelatin zymography and flow cytometry. The cell viability and adhesion were evaluated using methyl thiazol tetrazolium. In vivo, bilateral subrenal capsule xenograft transplantation of ameloblastoma was performed in 10 nude mice and the invasion of ameloblastoma into the renal parenchyma was observed. Results:  Active‐MMP‐2 of conditioned media was significantly lower in treatment group than in the control group. Accordingly, potential of in vitro cell invasion, adhesion and in vivo tumor invasion were also significantly lower in the treatment group than in the control group. Conclusions:  Inhibitor of MMP‐2 activity suppressed the local invasive capability of ameloblastoma by decreasing MMP‐2 activity. MMP‐2 activity is in relation with invasive capacity of ameloblastoma.