Function And Molecular Mechanism Of ADAM12 Involved In The Regulation Of Meningioma Invasion

Objective: The aim is to explore the expression level of ADAM12 in meningiomas,and to determine the association between ADAM12 expression and malignant biological behavior of meningiomas.Methods: Tumor samples were collected from 108 patients with meningiomas.Quantitative real-time polymerase chain reaction;immunohistochemistry and western blot were performed to examine the m RNA levels and protein expression levels of ADAMs in meningiomas.The correlation between the expression of ADAMs and clinicopathological features was analyzed.Results: 45 were male and 63 were female and the mean age at surgery was 51.9 years(range,10years-73years).Bone invasion was found in 18 of 108 patients through intraoperative observation.There were 47 patients with tumor diameters larger than 6 cm and 61 patients with tumor diameters less than or equal to 6 cm.Tumor location was divided into convexity(41 cases),parasagittal/falx(33 cases),skull base(27 cases),and other location(7 cases).The level expression of ADAM12 was correlated with the grade of meningioma and the invasion of the skull,but There was no significant correlation between ADAM12 expression and patient age,gender,tumor size,tumor location.ADAM12 is highly expressed specifically in malignant meningiomas(WHO III).Conclusion: Meningiomas invasiveness is closely associated with ADAM12 expression,which suggests that ADAM12 can serve as a biomarker of tumor invasiveness and a therapeutic target in meningiomas.Objective: To explore the role of ADAM12 and molecular mechanism promoting the aggressive feature of meningiomas.Methods: To investigate the effect of ADAM12 on the proliferation,invasion,migration and apoptosis of meningioma cells,we silenced and overexpressed ADAM12 with lentivirus in IOMM-Lee and CH157-MN cells.Receptor tyrosine kinase(RTK)phosphorylation protein microarray was used to detect and screen the signaling pathway to determine the potential molecular mechanisms of ADAM12 induced invasion of meningioma cells.Results: In IOMM-Lee and CH157-MN cell lines,the ability of migration,invasion and proliferation of tumor cells were significantly inhibited by ADAM12 silencing.In contrast,overexpression of ADAM12 can significantly enhance the ability of migration,invasion and proliferation of tumor cells.RTK phosphorylation microarray suggests that ADAM12 may exert biological effects through EGFR and AXL signaling pathways.Conclusion: ADAM12 regulates the proliferation,invasion and migration of meningioma cells through the EGFR and AXL signaling pathways.Objective: To verify the role and molecular mechanism of ADAM12 in promoting the invasion of meningioma in vivo.Methods: IOMM-Lee and CH157-MN cells transfected with lentivirus were subcutaneously injected to establish nude mice model of meningioma,and the tumor size was measured.The Ki-67 index and the expression level of ADAM12 in the xenograft tumors were detected by immunohistochemistry.Results: Overexpression of ADAM12 significantly increased tumor size,while the size was suppressed in ADAM12 knockdown group.In addition,Ki-67 index showed significant increases in ADAM12 overexpression group.In contrast,knockdown of ADMA12 downregulated the level expression of Ki-67.Conclusion: In the nude mice model of meningioma,the silencing of ADAM12 inhibited the growth of tumor,while the overexpression of ADAM12 promoted the growth and proliferation of meningioma cells in vivo.