Study On The Role And Mechanism Of Vasorin In Glioma Progression And Angiogenesis

Glioma,the most common human primary brain tumor,is characterized by proliferative and invasive capabilities.It is also one of the most vascularized tumors in the body.Glioma is hard to be surgically resected,and it is insensitive to radiotherapy and chemotherapy,which leads to poor prognosis.Therefore,it is crucial to explore the factors related to the malignant progression and angiogenesis of gliomas.Hypoxia is a critical factor in promoting tumor angiogenesis and induces the expression of the HIF-1 downstream gene Vasorin(VASN).VASN,a transmembrane glycoprotein,was proposed to play a role in vascular repair in early studies.Recently,VASN was found to be highly expressed in a variety of tumor tissues and promoted tumor cell proliferation.However,the role and mechanism of VASN in glioma progression and angiogenesis remains elusive.To investigate the role of VASN in glioma progression and angiogenesis,we first detected the expression of VASN in 100 clinical glioma samples by immunohistochemical staining.Results showed that the expression of VASN was elevated in high-grade gliomas,and the high expression of VASN was positively correlated with microvascular density(MVD)and shorter survival time of patients.To explore the regulatory effect of VASN on glioma cells,we established glioma cell lines with stable overexpression and knockdown expression of VASN.Results of CCK-8 cell proliferation assays,single-cell clonal expansion assays,and Transwell migration assays showed that glioma cells with high VASN expression had increased proliferation and invasion ability.Gene set enrichment analysis(GSEA)suggested that the gene expression of VASN was related to the signature of mesenchymal subtype gliomas and glioma angiogenesis.VASN can be secreted extracellularly,and the ELISA test showed that glioma cells with high VASN expression could secrete high-level VASN in the culture medium.The migration and tubule formation ability of human umbilical vein endothelial cells(HUVEC)treated with high VASN expression glioma medium was significantly enhanced.VASN was found to stimulate tumorigenesis and angiogenesis by chicken chorioallantoic membrane xenografts analysis.These results suggest that VASN could promote progression and angiogenesis in glioma.To further analyze the mechanism of VASN regulating the functions of glioma cells,we examined the effect of VASN on the expression of several signaling pathway-related proteins in glioma cells.Results showed that VASN could activate STAT3 and inhibit NOTCH1 signaling pathway-related proteins.Therefore,we conclude that VASN promotes glioma malignancy progression and angiogenesis by activating STAT3 and inhibiting NOTCH1 signaling pathway.In summary,we investigated the roles of VASN on glioma progression and angiogenesis,and preliminarily elucidated its related mechanisms.Our study provided an essential theoretical basis for basic research and clinical treatment of glioma.