TIMPs对舌鳞状细胞癌异常β-DG的作用

The roles of tissue inhibitors of metalloproteinases on aberrant β-DG in squamous cell carcinoma of the tongue

目的探讨金属蛋白酶组织抑制剂(TIMPs)对舌鳞状细胞癌异常β-肌营养不良蛋白聚糖(β-DG)的调控作用。方法用免疫组化SP和Western Blotting法,检测舌鳞状细胞癌Tca8113细胞株在MMP Inhibitor或MMP-2/MMP-9 Inhibitor调控前后异常β-DG改变情况。结果未用MMP Inhibitor或MMP-2/MMP-9Inhibitor调控前,舌鳞状细胞癌Tca8113细胞株无β-DG免疫特染区;调控后,癌细胞出现棕黄色β-DG免疫特染区。舌鳞状细胞癌Tca8113细胞株有43kDa和30kDa的β-DG蛋白条带;经MMP Inhibitor或MMP-2/MMP-9Inhibitor干预后,30kDa条带消失。结论 MMPs靶向作用Tca8113细胞株于癌细胞β-DG的近C端,使其断裂,从而使细胞与细胞外基质联结体断裂。经MMP Inhibitor或MMP-2/MMP-9 Inhibitor干预后,Tca8113细胞株癌细胞恢复了正常的β-DG;异常30kDa的β-DG消失。因此,MMP Inhibitor或MMP-2/MMP-9 Inhibitor能抑制舌鳞状细胞癌β-DG的断裂。另外,通过TIMPs抑制MMPs,能修复舌鳞状细胞癌断裂的β-DG蛋白,恢复癌细胞与细胞外基质的联结,从而可能会改变舌鳞状细胞癌侵袭和转移的特性。

Objective To probe the roles of tissue inhibitors of metalloproteinases（TIMPs） on aberrant β-DG in squamous cell carcinoma of the tongue.Methods MMP Inhibitor and MMP-2/MMP-9 Inhibitor were used to correct aberrant β-DG in Tca8113 cell line of squamous cell carcinoma of the tongue with immunohistochemistry and Western Blotting.Results There was no β-DG expression in Tca8113 cell line before TIMPs were used.Beta-DG expression restored when TIMPs were added into the culture media.Normally,β-DG was a single 43kDa band protein in normal tongue epithelium,on the contrary,there were 43kDa and 30kDa bands in Tca8113 cell line.The 30kDa β-DG disappeared in Tca8113 cell line when TIMPs were added.Conclusion The connection between cell and extra cell matrix is ruptured at the location of β-DG.TIMPs can restore the ruptured β-DG.The ruptured connection may be the reason of invasion and metastasis in squamous cell carcinoma of the tongue.