Study of degradation mechanism of extracellular matrix in oral cancer and possible development of matrix metalloproteinase inhibitors as anticancer drugs

(A)本研究旨在探讨MMP和TMP在口腔鳞癌发生发展中的作用。1)SCC细胞株在体外培养和裸鼠舌内移植后，转移细胞株MMP-1、MMP-2、MMP-9和MT-MMP的表达均强于非转移细胞株。2)用明胶酶谱法和光密度法测定匀浆中明胶的水解活性。高转移病例的细胞系组织标本和裸鼠舌移植组织标本中MMP-2和MMP-9的明胶溶解活性增强。因此，这些结果表明，肿瘤的进展是依赖于肿瘤细胞降解细胞外基质（ECM）的能力，而肿瘤的转移是由许多类型的MMPs调节，因此，MMPs的过度生产似乎是更重要的转移比生产的TIMPs在体内。(B)为了研究基质金属蛋白酶抑制剂作为抗癌药物的可能性，我们将移植了SCC细胞系的裸鼠分为两组，抗癌药物组：给予抗癌药物的小鼠组，对照组：未给予抗癌药物的小鼠组。1)抗癌药物组肿瘤体积小于对照组。2）移植瘤组织中MMP、TIMP的表达。抗肿瘤药物组MMPs和TIMPs的表达均低于对照组。

(A) We studied the roles of MMP and TMP in metastastic mechanisms of oral squamous cell carcinoma. 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-1, -2, -9 and MT-MMP than the non-metastatic cell lines. 2) The gelatinolytic activities in the homogenates were measured by gelatin zymography and its densitometric analysis. Highly metastatic cases 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. 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 than the production of TIMPs in vivo.(B) We studied possible development of matrix metalloproteinase inhibitors as anticancer drugs.We divided nude mice which were transplanted SCC cell lines into two groups, anticancer drugs group : the groups of mice which were given anticancer drugs, control groups : the groups of mice which were not given anticancer drugs. 1) Tumors size of anticancer drug groups was smaller than control groups. In anticancer drug groups, cervical lymph metastasis were not found. 2) MMP and TIMP expression was examined in transplanted tumors. In anticancer drugs group, a lower expression of MMPs and TIMPs were recognized than in control groups.