Sequential MMP-2 Alteration in DMBA-Induced Hamster Cheek Pouch Carcinogenesis

The matrix metalloproteinases (MMPs) are produced by the cancer cells or through induction of surrounding stromal cells. The ability of MMP-2 to degrade basement membrane type IV collagen appears especially important in cancer progression. However, the sequential alteration of MMP-2 in oral carcinogenesis has not yet been well demonstrated. Objective: The aim of this study was to investigate the sequential MMP-2 alteration in DMBA-induced hamster cheek pouch model. Methods: Thirty-seven out-bred, young (7 weeks old), male Syrian golden hamsters were randomly divided into 5 experimental groups (week 4, 6, 8, 10, and 12 DMBA treated groups; each with 5 animals) and two control groups (6 animals each). The pouches of each experimental group were bilaterally painted with a 0.5% DMBA solution three times a week. Each animal of one control group was similarly treated with mineral oil only, while the other control group remained untreated throughout the experiment. All pouches were studied both grossly and histologically. Tissues from each group were used to evaluate MMP-2 activity by gelatin zymography. Results: The main gelatinase secreted by hamster cheek pouch migrated at 72 kDa and represented MMP-2. The values of MMP-2 activity were found increased in a time-dependent manner (p<0.05). From the AlphaImager 2000 densitometer, the amount of MMP-2 was about 1.7 fold on week 4 (hyperkeratosis), 3.1 fold on week 6 (dysplasia), 5.8 fold on week 10 (leukoplakia), and 8.4 fold on week 12 (carcinoma) compared with control, respectively. Conclusion: These results demonstrate that the up-regulation of MMP-2 expression in DMBA-induced oral carcinogenesis, suggesting that MMP-2 may play an important role in the pathogenesis of oral cancer.