Prosaposin promotes the proliferation and tumorigenesis of glioma through toll-like receptor 4 (TLR4)-mediated NF-κB signaling pathwayResearch in context
Yang Jiang,
Jinpeng Zhou,
Peng Luo,
Huiling Gao,
Yanju Ma,
Yin-Sheng Chen,
Long Li,
Dan Zou,
Ye Zhang,
Zhitao Jing
Affiliations
Yang Jiang
Department of Neurosurgery, The First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang City 110001, China
Jinpeng Zhou
Department of Neurosurgery, The First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang City 110001, China
Peng Luo
Department of Neurosurgery, The First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang City 110001, China
Huiling Gao
College of Life and Health Sciences, Northeastern University, Shenyang, China
Yanju Ma
Department of Medical Oncology, Cancer Hospital of China Medical University, Shenyang 110042, China
Yin-Sheng Chen
Department of Neurosurgery/Neuro-oncology, SunYat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
Long Li
Department of Neurosurgery, The First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang City 110001, China
Dan Zou
The First laboratory of cancer institute, The First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang City 110001, China
Ye Zhang
The First laboratory of cancer institute, The First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang City 110001, China; Corresponding author at: The First laboratory of cancer institute, The First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang City 110001, China.
Zhitao Jing
Department of Neurosurgery, The First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang City 110001, China; Corresponding author at: Department of Neurosurgery, The First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang City, 110001, China.
Background: As a neurotrophic factor, prosaposin (PSAP) can exert neuroprotective and neurotrophic effects. It is involved in the occurrence and development of prostate and breast cancer. However, there is no research about the role of PSAP in glioma. Methods: The PSAP overexpressed or silenced glioma cells or glioma stem cells were established based on Lentiviral vector transfection. Cell viability assay, Edu assay, neurosphere formation assay and xenograft experiments were used to detect the proliferative ability. Western blot, Elisa and luciferase reporter assays were used to detect the possible mechanism. Findings: 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. Interpretation: 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. Fund: This work was funded by National Natural Science Foundation of China (Nos. 81101917, 81270036, 81201802, 81673025), Program for Liaoning Excellent Talents in University (No. LR2014023), and Liaoning Province Natural Science Foundation (Nos. 20170541022, 20172250290). The funders did not play a role in manuscript design, data collection, data analysis, interpretation nor writing of the manuscript. Keywords: Glioma, Glioma stem cells, Prosaposin, Proliferation, Tumorigenesis
