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

(A)研究基质金属蛋白酶及其组织抑制因子(TIMP)在口腔鳞癌(OSCC)细胞系转移机制中的作用。MT1-MMPs和TIMP基因。结果：1)无论是体外培养的SCC细胞系，还是裸鼠舌下移植的SCC细胞系，转移细胞系的MMP2、MMP9和MT1-MMPs的表达均较未转移细胞系强。2)转移细胞系移植于裸鼠舌体后，其组织标本中的明胶溶解活性增强。3)转染人基质金属蛋白酶-2、-9和MT1-基质金属蛋白酶基因的未转移细胞系具有转移活性，并在颈淋巴结内转移。这些转移活性可被基质金属蛋白酶抑制剂抑制。4)在转导TIMP-1、TIMP-2基因的转移细胞系中，未发现颈淋巴转移。这些结果表明，肿瘤的进展依赖于肿瘤细胞降解细胞外基质(ECM)的能力，而肿瘤的转移受多种类型的MMPs的调节，因此MMPs的过度生产在体内转移中显得更为重要。(B)我们研究了基质金属蛋白酶抑制剂对基质金属蛋白酶的可能抑制作用。我们将移植SCC细胞的裸鼠分为两组，I组：给予基质金属蛋白酶抑制剂的组，对照组：不给予基质金属蛋白酶抑制剂的组。结果：1)I组肿瘤体积小于对照组。I组无颈淋巴转移。2)移植瘤组织中可检测到基质金属蛋白酶和Tump的表达。I组MMPs和TIMPs的表达低于对照组。提示基质金属蛋白酶抑制剂可显著抑制小鼠颈淋巴转移和基质金属蛋白酶的活化。

(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