S100A4 Expression is Closely Linked to Genesis and Progression of Glioma by Regulating Proliferation, Apoptosis, Migration and Invasion

Abstract

<b>Background:</b> The calcium-binding S100A4 protein is involved in epithelial to mesenchymal transition,oncogenic transformation, angiogenesis, cytoskeletal integrity, mobility and metastasis of cancer cells. Thisstudy aimed to clarify the roles of S100A4 in genesis and progression of glioma. Materials and <br/><b>Methods</b>: S100A4expression was examined by real-time RT-CPR and Western blot in glioma and paired normal brain tissue(n=69), and compared with clinicopathological parameters of tumors. In addition, glioma U251 cells transfectedwith an S100A4-expressing plasmid were examined for proliferation by MTT, apoptosis by Annexin V-FITC,and migration and invasion with Transwell chambers. <br/><b>Results</b>: Increased S100A4 mRNA expression was foundin gliomas, compared with paired non-tumor tissue (p<0.001). Gradual elevation of overexpression of S100A4was observed with increasing glioma grade (p<0.001). Astrocytoma showed lower S100A4 mRNA expressionthan oligodendrogliomas, with glioblastomas having highest values (p<0.001). Similar results were obtained forS100A4 protein, a positive link being found between mRNA and protein expression in gliomas (p<0.001). Therewas higher growth, lower apoptosis, stronger migration and invasion of S100A4 transfectants than control andmock transfected cells (p<0.001). <br/><b>Conclusions</b>: These findings indicate that up-regulated S100A4 expression ispositively linked to pathogenesis, progression and histogenesis of glioma by modulating proliferation, apoptosis,migration and invasion.