侵袭转移相关因子在胃肠道间质瘤中的检测及其意义

Significance of expression of metastasis-related factors uPA,MMP-2,MMP-9 and TGF-β1 in gastrointestinal stromal tumors

目的:研究uPA、MMP-2、MMP-9、TGF-β1等侵袭转移相关因子在胃肠道间质瘤(GISTs)中的表达及其临床病理意义.方法:应用RT-PCR及Westernblot法检测uPA、MMP-2、MMP-9、TGF-β1在124例GISTs中的表达.结果:在GISTs中,随着NIH分级增高,uPA、MMP-2、MMP-9、TGF-β1的mRNA表达水平上调,低、中、高危组有明显差异(P<0.05或0.01),其阳性表达率与性别、年龄、组织学类型无关,与肿瘤侵袭转移和黏膜受侵关系密切;四者的蛋白表达水平与mRNA表达一致;uPA与TGF-β1蛋白阳性表达之间呈显著正相关(r=0.356)、uPA与MMP-2、MMP-9蛋白阳性表达之间亦呈显著正相关(r=0.323,0.346).结论:TGF-β1、uPA、MMP-2及MMP-9参与了GISTs的浸润和转移;TGF-β1可能通过上调uPA,激活MMP-2及MMP-9,进而降解细胞外基质.

AIM：To investigate the significance of expression of urokinase-type plasminogen activator （uPA）,matrix metalloproteinase-2 （MMP-2）,matrix metalloproteinase-9 （MMP-9） and transforming growth factor-β1 （TGF-β1） in gastrointestinal stromal tumors （GISTs）.METHODS：The expression of uPA,MMP-2,MMP-9 and TGF-β1 mRNAs and proteins in 124 GISTs specimens was detected by reverse transcription-polymerase chain reaction （RT-PCR）and Western blot,respectively.RESULTS：In gastrointestinal stromal tumors,the mRNA expression of uPA,MMP-2,MMP-9 and TGF-β1 is closely correlated with tumor stage （NIH classif ication）,mucosal invasion and lymphatic metastasis.The mRNA expression levels of uPA,MMP-2,MMP-9 and TGF-β1 were up-regulated with increasing tumor stage,showing significant differences among low-,moderate-and high-risk GISTs.The positive rates of uPA,MMP-2,MMP-9 and TGF-β1 mRNA expression was not correlated with age,sex and histological type.Similar results were obtained for the expression of uPA,MMP-2,MMP-9 and TGF-β1 proteins in GISTs.The expression of uPA protein is positively correlated with that of TGF-β1,MMP-2 and MMP-9 （r=0.356,0.323 and 0.346,respectively）.CONCLUSION：The positive activation of TGF-β1 in GISTs possibly up-regulates uPA expression which in turn activates MMP-2 and MMP-9.The activation of MMP-2 and MMP-9 may lead to the degradation of extracellular matrix degradation and promote tumor invasion and metastasis.