Study of roles of matrix metalloproteinase (MMP) and tissue inhibitor of MMP (TIMP) in metastastic mechanisms of oral squamous cell carcinoma (OSCC) cell line.

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(A) We studied the roles of matrix metalloproteinase (MMP) and tissue inhibitor of MMP (TIMP) in metastastic mechanisms of oral squamous cell carcinoma (OSCC) ceil lines which were transfected MMP-2, -9. MT1-MMP and TIMP gene. Results : 1) When SCC cell lines were either cultured in vitro or transplanted in the tongue of nude mice, the metastatic cell lines tended to show a stronger expression of MMP-2, -9 and MT1-MMP than the non-metastatic cell lines. 2) The metastatic cell lines showed the increased gelatinolytic activities of MMP-2 and MMP-9 in the tissue specimens of cell line and transplanted in the tongue of nude mice. 3) The non-metastatic cell lines which were transfected MMP-2, -9 and MT1-MMP gene showed metastatic activity and matastasized in cervical lymph node. These metastatic activity were inhibited by MMP inhibitor. 4) In the metastatic cell lines, which were transfected TIMP-1, -2 gene, cervical lymph metastasis were not found. These results therefore suggest that tumor progression is dependent on the ability of tumor cells to degrade extracellular matrix (ECMs), while the metastasis of tumors is regulated by many types of MMPs, and the overproduction of MMPs therefore appears to be more important for metastasis t in vivo.(B) We studied possible inhibition of matrix metalloproteinase by MMP inhibitor. We divided nude mice which were transplanted SCC cell lines into two groups, Group I : the groups of mice which were given MMP inhibitor, control groups : the groups of mice which were not given MMP inhibitor. Results : 1) Tumors size of Group I was smoller than control groups. In Group I, cervical lymph metastasis were not found. 2) MMP and TUMP expression was examined in tranplanted tumors. In Group I, a lower expression of MMPs and TIMPs than control groups. These rusult suggest that cervical lymp node metastasis and activation of MMP were significantly suppressed by MMP inhibitor