|Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥1,600,000 (Direct Cost: ¥1,600,000)
In order to study the roles of matrix metalloproteinases (MMPs) in lymph node metastasis of oral squamous cell carcinoma (SCC), the expression of MMP-1 (tissue collagenase), MMP-2 (72kDa gelatinase/type IV collagenase), MMP-3 (stromelysin-1), MMP-9 (92kDa gelatinase/type IV collagenase) and TIMP-1 (tissue inhibitor of metalloproteinase-1) in oral SCC tissues obtained from biopsy specimens of 46 cases and from in vivo metastasis model was examined immunohistochemically or biochemistrically. Among these MMPs, MMP-1 and MMP-9 were immunolocalized in the carcinoma cells in 70.0% and 45.7% of oral SCC,respectively. On the other hand, MMP-2 and MMP-3 were positively stained only in 21.1% and 10.5%, respectively. TIMP-1 was immunolocalized in 22.2% of the cases, but the ratio of immunoreactive cells to the total carcinoma cells was only 0.6(]SY.+-.])0.2%. The ratio of positive cells for MMP-1 or MMP-9 in carcinomas with lymph node metastasis was significantly higher than that in carcinomas without metastasis. In in vivo metastasis model, gelatinolytic activity was higher in the culture media of OSC-19 cells (high metastatic phenotype) than that of OSC-20 cells (low metastatic phenotype). Gelatin-substrate gel electrophoresis also showed that the gelatin-degrading activity with molecular weight of 92.000 was higher in the culture media of OSC-19 cells than that of OSC-20 cells. These results suggest that MMP-1 and MMP-9 play pivotal roles in the degradation of extracellular matrix macromolecules during oral SCC metastasis.