Role of the matrix-degrading enzymes and their inhibitors on invasion and metastasis of oral SCC

我们检测了明胶酶及其抑制物在口腔鳞状细胞癌BHY(非转移性)和HN(转移性)细胞中的表达。两个细胞都表达几种明胶酶。此外，BHY细胞分泌原MMP7和原L蛋白，而HN细胞分泌大量活性MMP2。HN细胞可分泌TIMP1，但仅有少量TIMP2。癌细胞分泌的基质金属蛋白酶2和组织蛋白酶L的净活性可能分别与口腔癌细胞的淋巴转移和骨侵袭有关。癌细胞巢中的明胶溶解活性明显高于正常牙龈上皮。转移癌癌细胞巢中活性MMP2活性显著高于未转移癌(p&lt；0.05)。我们还用RT-PCR检测了口腔鳞癌患者外周血中循环癌细胞的存在，检测了12例口腔鳞癌患者中11例呈阳性结果。但血源性CK20基因与肿瘤转移的关系尚不明确。所有无瘤幸存者的检测结果均为阴性。肿瘤细胞中活性MMP2的表达可作为预测肿瘤转移的指标，外周血中CK20mRNA的表达可作为口腔鳞癌患者肿瘤复发的指标。然后我们分析了该基因在口腔癌转移潜能中的作用。但TSC-22正、反义基因均不影响TYS细胞的转移潜能。转移性口腔癌与非转移性口腔癌组织中TSC-22mRNA的表达差异无统计学意义。

We examined the expression of gelatinases and their inhibitors in human oral SCC cells, BHY (non-metastatic) and HN (metastatic). Both of the cells expressed several gelatinases. In addition, BHY cells secreted proMMP7 and procathepsin L,while HN cells secreted a large amount of active MMP2. HN cells secreted TIMP1, but only a trace level of TIMP2. The net activity of MMP2 and cathepsin L secreted from cancer cells may contribute respective to lymph node metastasis and the bone invasion of oral cancer cells.We examined the gelatinases in human oral SCC tissues by a microdissection-zymography. The gelatinolytic activities in cancer cell nests were much higher than those of normal gingival epithelium. The activities of active-MMP2 in cancer cell nests of metastatic cancers were significantly higher than those of non-metastatic cancers (p<0.05). We also examined the existence of circulating cancer cells in the peripheral blood of oral SCC patients by RT-PCR for cytokeratin 20 (CK20) mRNA.Eleven of 12 oral SCC patients showed positive results. However, there is no clear relationship of hematogenous CK20 mRNA for metastasis. All of the tumor-free survivors showed negative results. The expression of active-MMP2 in cancer cells can be used as a predictive marker for metastasis, and CK20 mRNA in peripheral blood can be used as a marker for tumor-recurrence in oral SCC patients.We isolated a growth suppressor gene, TSC-22. Then we analyzed the role of the gene on metastatic potentials of oral cancers. However, transfection of either sense or antisense TSC-22 gene did not affect the metastatic potentials of TYS cells. Futhermore, there was no significant difference in the expression of TSC-22 mRNA between metastatic oral cancers and none-metastatic oral cancers.