The Potential Mechanism Of High Mobility Group Box 1 Protein On Meningioma Pathogenesis And Invasion

Objective:High mobility group box 1 protein(HMGB1)is highly expressed in malignant cells,which is closely associated with tumor malignization and invasiveness.The present study was performed to determine the expression patterns of HMGB1 in meningiomas,and to clarify the potential mechanism of pathogensis and invasiveness of meningiomas,in turns to provide a new strategy for preventing and treating meningiomas.Methods:Fifty-six intracranial,totally resected benign and malignant meningiomas and ten normal brain tissuer were divided into there groups as follows:①in normal control group(n=10);②in benign group(WHOⅠgrade, n=50);③in malignant group(WHOⅢgrade,n=6).Samples of meningioma and normal brain tissue were harvested sterilely and divided into two parts:one part was detected expression of HMGB1,MMP-9,and VEGF by RT-PCR, western-blot and immunohisochemical analysis,and was determined activation of Cdc-42 with Western blot.The other part was prepared for cell culture.The cell proliferation was measured by MTT method,and cell apoptosis and cell cycle were observed with flow cytometry(FCM).Result:1.The expression of HMGB1 in meningiomas:(1)Compared with normal and benign group,the HMGB1 protein increased dramatically in malignant group(P＜0.05 or P＜0.01).However there was no significantly different between the normal group and benign group.(2)The mRNA expression of HMGB1 was significantly elevated in malignant group(P＜0.01),compared with the normal and benign groups.There was a significant different between normal and benign group(P＜0.05).(3)The expression of HMGB1 mRNA was coincident with that of HMGB1 protein in the malignant group.2.The effect of HMGB1 on meningioma invasiveness:(1)The mRNA expression of MPP-9 and VEGF was significantly elevated in malignant group(P＜0.05 or P＜0.01), compared with the normal and benign groups.(2)The protein amount of MMP-9 and VEGF identifyied by immunohisochemistry in malignant group was higher than normal and benign group(P＜0.05),but there was no significant difference between the normal and benign groups.(3)The activation of Cdc-42 in malignant group was increased compared with normal and benign group(P＜0.05).(4) There was significantly correlation between the mRNA expression of MMP-9 and VEGF and the HMGB1 in malignant group.3.Effect of HMGB1 on the apoptosis,cell proliferateion and cell cycle:(1)MTT measurement demonstrated that the malignant group had a higher cell proliferation and a more decreasing apoptosis rate than the benign group(P＜0.05).(2)The G1 phase fraction(90%)in benign group was more than 10%in the malignant group (80%).The G2+S phase fraction(19.5%)in the malignant group was more than 8%in the benign group(11.7%).(3)The expression of HMGB1 mRNA was correlated with cell proliferation and apoptosis rate.Conclusions:1.The overexpression of HMGB1 may play a critical role in the pathogensis and invasiveness of meningiomas.2.The high expression of HMGB1 is correlated with the overexpression of MMP-9 and VEGF.HMGB1 may play an important role in the angiogenic and invasive processes in malignant meningiomas.3.HMGB1 may regulates cell migration and induce the invasive behaviour of malignant meningioma cell.4.HMGB1 may influence cell proliferateion and apoptosiss,and in turn induce pathogensis of meningiomas.