uPAR促进恶性脑膜瘤细胞的侵袭

uPAR promotes malignant meningioma cells invasion

目的探索脑膜瘤中尿激酶型纤溶酶原激活物(uPA)及其受体(uPAR)表达水平与病理等级间关系;探索uPAR在恶性脑膜瘤中的功能及其机制。方法通过检测各等级脑膜瘤临床标本中uPAR和uPA表达水平,分析其表达量与病理等级间关系。通过体外实验干扰uPAR表达,观察恶性脑膜瘤细胞侵袭能力的变化,并检测细胞中侵袭相关因子MMP2、MMP9及E-cadherin的表达变化。结果临床标本中脑膜瘤病理等级越高uPAR和uPA的蛋白表达量也越高:在Ⅰ级脑膜瘤组织中均以弱阳性表达为主(uPA占73.30%,uPAR占66.66%);Ⅱ级脑膜瘤组织中均呈弱阳性(uPA占37.50%,uPAR占18.75%)、中阳性(uPA占37.50%,uPAR占43.75%)、强阳性(uPA占25.00%,uPAR占37.50%)均衡表达;Ⅲ级脑膜瘤组织中均以强阳性(uPA占66.6%,uPAR占83.33%)表达为主。干扰uPAR表达后,脑膜瘤细胞侵袭能力明显降低,细胞中侵袭相关因子MMP2、MMP9的蛋白表达也明显降低。结论 uPA-uPAR表达在脑膜瘤中,其表达量与脑膜瘤的恶性等级成正相关;uPAR对恶性脑膜瘤细胞有促侵袭功能,该功能可能通过调控MMP2和MMP9的表达来实现的。

Objective To explore the relationships among tumor grade and levels of urokinase-type plasminogen activator（uPA） or its receptor（uPAR） in meningiomas.The function of uPAR and its molecular mechanisms in malignant meningiomas were also studied .Methods We detected the protein levels of uPAR and uPA in 58 samples of meningiomas to analyze whether the protein levels of uPAR/uPA were related to tumor grade of meningiomas .The expression of uPAR to study whether uPAR affects the invasion of malignant meningioma cells and the expression levels of invasive molecules （ MMP-2 , MMP-9 and E-cadherin ） were knocked down .Results The protein levels of uPAR and uPA was proportional to malignant degree of meningiomas .In normal brain tissues ,uPAR and uPA were not detected , in grade Ⅰ meningiomas , uPAR and uPA were mainly weekly stained （ week：uPA 73 .30%, uPAR 66 .66%） .In grade Ⅱ meningiomas , uPAR and uPA were equably stained in each grade meningiomas （ week：uPA 37.50%,uPAR 18.75%,moderate：uPA 37.50%, uPAR 43.75%;strong：uPA 25.00%,uPAR 37.50%）.In grade Ⅲ meningiomas,uPAR and uPA were mainly strongly stained （ strong：uPA 66.6%,uPAR 83.33%）.Knockdown of uPAR did not affect the expression of uPA , but strongly decreased the levels of MMP-2 and MMP-9 .Knockdown of uPAR also decreased the invasion of malignant meningioma cells .Conclusion The uPA-uPAR system was extensively expressed in meningiomas , and its expression level was proportional to malignant degree of meningiomas .uPAR shows ability to increase the invasion of malignant meningioma cell by regulating MMP2 and MMP9.