The Mechanism Of Periostin To Promote The Invasion And Proliferation Of Malignant Mengingiomas

Background and purposeMeningiomas are the most common neuroepithelial tumors that originate from the arachnoid cap cells.The vast majority of meningiomas are benign tumors(BMs,WHO I),but atypical meningiomas(AMs,WHO II)and malignant meningiomas(MMs,WHO ?)accounted for the proportion of up to 25%.The prognosis of malignant meningiomas is the worst.The median survival of malignant meningiomas is only 1.5 years which overall recurrence rate is as high as 80%.In order to improve the prognosis of malignant meningiomas,it is crucial to search for a effective treatment.Our previous study found that periostin(POSTN)expression was statistically different between BMs and MMs.Therefore,we considerate that POSTN could be a novel factor to predict the prognosis of mingiomas.As a extracellular matrix protein,POSTN combined with integrins on the surface of the cell membrane to regulate the steady state of tumor microenvironmet(TME).POSTN also causes the epithelial-mesenchymal transition to promote the invasion and proliferation in virous tumors.But there is no report describe the mechanism or functions of POSTN in meningiomas.Our study aims to investigate the role of POSTN in the malignant behavior of meningiomas.Understanding the key protein and signal pathway will provide new ideas to find a effective treatment for MMs.Contents and methods1.In vitro culture and identification of primary cells of MMsFresh samples were collected for primary cell culture and purification,observe the primary cell morphology and test the proliferation.Immunofluorescence was used to identify meningioma cells.2.The study of periostin in malignant meningioma cells' malignant phenotype and cell fuctions.Different levels of meningioma tissue were tested by qRT-PCR and Western blot,POSTN expression in immunohistochemical method to observe POSTN degree and expressed by different level meningioma in the site,expressed in malignant meningioma in the Spearman correlation test to detect POSTN relevance to meningiomas invading,Western blot detection of the expression of POSTN in purificatory malignant meningioma cells and tumor associated fibroblasts.3.Study on the mechanism of POSTN influencing the malignant phenotype of malignant meningioma cells.The cells were were transfected with POSTN or empty vectors.EMT related proteins were detected by Western blotting.The cell proliferation wsa detected by CCK8.The invasion and migration ability of POSTN cells were detected by Transwell chamber motion test.The tumorigenic ability of the two groups was detected by nude mice.Results1.The meningioma cells identified EMA and Vimentin expression positive,the proliferation ability of malignant meningioma cells is stronger than benign meningioma cells,beta galactose glucoside enzyme staining positive rate of benign meningioma cells is higher.2.The POSTN expression of protein and mRNA level of MMs was higher than BMs(P<0.01),POSTN was associated with a significant malignant meningiomas invading(r = 0.738,P<0.001),POSTN is expressed in the stroma of malignant meningioma,the expression of POSTN in tumor associated fibroblasts is higher than that in meningioma cells(P<0.01).3.E-cadherin was significantly downregulated in POSTN-overexpressed meningioma cells(P<0.001),N-ca.p-Akt.Vimentin.Snail were significantly upregulated,proliferation and invasive ability was enhanced(P<0.001).ConclusionCompared with the LGMs,HGMs have a stronger ability to proliferate and behave more aggressively,which results in the worse prognosis of MMs.POSTN,the extracellular matrix protein,secreted by CAFs in HGMs may be a key protein that regulates the malignant behavior of MMs.POSTN activate the Akt signal pathway which promote the EMT of tumors.Therefore,targeting therapy for this regulatory mechanism may provide a new potential target for the comprehensive treatment of HGMs and improve its prognosis.