基质金属蛋白酶及其抑制剂与口腔鳞癌颈淋巴结转移的关系

目的:探讨基质金属蛋白酶-2,9(MMP-2,9)和基质金属蛋白酶抑制剂-1,2(TIMP-1,2)在口腔鳞癌中的表达形式以及其活性与颈淋巴结转移的关系。方法:应用原位杂交法(in situ hybridization,ISH)检测30例口腔鳞癌组织,口腔鳞癌转移细胞系GNM和人舌鳞癌细胞系TSCCa MMP-2,9和TIMP-1,2的表达;应用胶质酶谱法(zomography)分析上述标本MMP-2,9的活性以及应用体外侵袭实验检测两细胞系侵袭力的差异。结果:MMP-2,9和TIMP-1,2 mRNA 在肿瘤细胞和间质细胞均有表达;有转移鳞癌组织MMP-2,9,以及TIMP-1,2阳性率均高于无转移患者(P<0105), GNMMMP-2,9阳性率高于TSCCa;MMP-2,9活性在转移组明显高于未转移组(P<0105);GNM条件培养上清液中 MMP-2,9活性以及体外侵袭力均高于TSCCa。结论:MMP-2,9在口腔鳞癌转移中有重要作用,TIMP-1,2表达上升可能是肿瘤细胞与间质相互作用的结果。

The Effects of MMPs and TIMPs on the Metastasis of Oral Squamous Cell Carcinoma to Neck Lymph Nodes

Objective:This study is aim at investigating the relationship between the expression and activity of MMP_2,9, TIMP_1,2 and the metastasis of oral squamous cell carcinoma to neck lymph node. Methods: The expression of MMP_2,9, TIMP_1,2 in 30 oral squamous cell carcinoma, two oral squamous cell carcinoma cell lines GNM and TSCCa was detected by in situ hubridization; Zomography was performed to determined the activity of MMP_2,9 in cancer tissue and conditioned medium of GNM and TSCCa; Ability of invasion of GNM and TSCCa was measured with in vitro invasion assays. Results: Both tumor cells and stroma expressed both MMP_2,9 and TIMP_1,2; It was found that MMP_2,9, TIMP_1,2 had a higher expression in patients with neck lymph node metastasis than those without metastasis (P<0 05), positive percentage of MMP_2,9 in GNM was higher than that in TSCCa; The MMP_2,9 in node_positive patients was more active than in node_negative ones (P<0 05); GNM had more active MMP_2,9 and higher invasive potential than TSCCa. Conclusion: MMP_2,9 may play an important role in metastasis of oral squamous cell carcinoma; Elevation of TIMP_1,2 is likely to be the result of interaction of tumor and stroma.