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)本实验通过转染基质金属蛋白酶（MMP-2）、基质金属蛋白酶组织抑制剂（TIMP），研究MMP-2、MMP-9在口腔鳞癌细胞系中的表达及其在口腔鳞癌发生、发展中的作用。MT1-MMP和TIMP基因。结果如下：（1）SCC细胞系无论是体外培养还是裸鼠舌内移植，转移细胞系MMP-2、MMP-9和MT1-MMP的表达均强于非转移细胞系。2)转移瘤细胞株的组织标本和裸鼠舌内移植瘤组织标本中MMP-2和MMP-9的明胶分解活性增强。3)转染MMP-2、MMP-9和MT1-MMP基因的非转移细胞株具有转移活性，并在颈淋巴结中发生转移。MMP抑制剂可抑制这些转移活性。4)在转染TIMP-1、TIMP-2基因的转移细胞系中，未发现颈淋巴结转移，提示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MMPs的调节，MMPs的过度产生对肿瘤的转移比体内转移更为重要。(B)我们研究了MMP抑制剂对基质金属蛋白酶的可能抑制作用。我们将移植了SCC细胞系的裸鼠分为两组，I组：给予MMP抑制剂的小鼠组，对照组：未给予MMP抑制剂的小鼠组。结果：1）实验组肿瘤体积小于对照组; 2）MMP和TUMP在移植瘤中的表达; I组MMPs和TIMPs的表达均低于对照组。提示MMP抑制剂能明显抑制宫颈淋巴结转移和MMP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