The Effect And Mechanism Of Podoplanin On Malignant Behavior Of Glioma Cells

Background and objective:The high proliferation and invasion potential of glioma greatly increases the difficulty of its treatment.At present,the main treatment methods for glioma include tumor resection,radiotherapy and chemotherapy and so on.However,the survival rate of glioma patients is still very low,and there are still many challenges in the treatment of glioma,so new therapeutic targets need to be found.In recent years,studies have shown that the expression of podoplanin（PDPN）is up-regulated in glioma,and there is a correlation between high PDPN expression and shorter overall survival（OS）in astroglioma patients.PDPN is a transmembrane glycoprotein with elevated expression in a variety of tumors.Scientific research has confirmed that PDPN plays an important role in tumor-related thrombosis,tumor progression,tumor invasion and migration.In recent years,there has been some controversy about role of PDPN in gliomas.Our study aimed to explore PDPN expression in glioma tissues and the potential mechanism of PDPN on the malignant behavior of glioma cells,so as to provide experimental basis for new therapeutic targets for gliomas.Methods:The expression levels of PDPN in brain glioma tissues and adjacent normal tissues were determined by immunohistochemistry.LN18,U87 and U118 glioma cells with different expression of PDPN were selected for cytological experiments.Small interfering RNAs（si RNAs）were used to transfect U87 and U118 glioma cells to silence the expression of PDPN.The plasmid carried PDPN gene was used to transfect LN18 glioma cells to upregulate the expression of PDPN.Flow cytometry,Western blotting and Transwell experiments were used to probe the influences of PDPN on the cell cycle and invasion and migration of glioma cells,and the possible molecular mechanisms were explored.Results:1.Compared with normal brain tissues,the expression of PDPN increased distinctly in high-grade glioma tissues,while not in low-grade glioma tissues.2.Knockdown of PDPN affected the cell cycle of U118 and U87 glioma cells,and both of the cells were blocked in G2/M phase.3.Knockdown of PDPN reduced the invasion and migration of U118 and U87 glioma cells,while increasing the expression of PDPN enhanced the invasion and migration of LN18 glioma cells.4.After knockdown of PDPN,the EMT-related marker proteins in U118 and U87 glioma cells did not change significantly,but the levels of MMP2 and MT1-MMP declined obviously,and the phosphorylation of ERM proteins related to cytoskeleton and motion decreased clearly.The opposite results were observed after upregulation of PDPN in LN18 glioma cells.5.Knockdown of PDPN could decrease the expression of MAPK/ERK signaling pathway-related proteins,while upregulation of PDPN could increase the expression levels.Conclusions:1.The expression of PDPN in high-grade glioma tissues was significantly higher than in normal brain tissues,suggesting that PDPN may be related to the malignant behavior of glioma.2.PDPN can affect the proliferation,invasion and migration of glioma cells.3.PDPN may affect the proliferation,invasion and migration of glioma cells through MAPK/ERK signaling pathway.