Prosaposin Promotes the Proliferation and Tumorigenesis of Glioma Through Toll-Like Receptor 4 (TLR)-Mediated NF-Κb Signaling Pathway

Abstract

Prosaposin (PSAP) is a conserved glycoprotein, which is found to express in brain, acting as neurotrophic factor. Recent studies have demonstrated that overexpression of PSAP is related to the occurrence and development of prostate cancer and breast cancer. However, there is no research about the role of PSAP in glioma. Our study firstly found that PSAP was highly expressed and secreted in clinical glioma specimens, glioma stem cells, and glioma cell lines. It was associated with poor prognosis. We found that PSAP significantly promoted the proliferation of glioma stem cells and cell lines. Moreover, PSAP promoted tumorigenesis in subcutaneous and orthotopic models of this disease. Furthermore, GSEA and KEGG analysis predicted that PSAP acts through the TLR4 and NF-κB signaling pathways, which was confirmed by western blot, immunoprecipitation, immunofluorescence, and use of the TLR4-specific inhibitor TAK-242. The findings of this study suggest that PSAP can promote glioma cell proliferation via the TLR4/NF-κB signaling pathway and may be an important target for glioma treatment. Funding: This work was funded by Chinese National Foundation of National Sciences (Nos. 81101917, 81270036, 81201802, 81673025), Program for Liaoning Excellent Talents in University (No. LR2014023), and Liaoning Province Natural Science Foundation (Nos. 20170541022, 20172250290). Declarations of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: This study was approved by the ethics committee of the First Affiliated Hospital of China Medical University and written informed consent was obtained from each patient.