Prosaposin promotes the proliferation and tumorigenesis of glioma through toll-like receptor 4 (TLR4)-mediated NF-κB signaling pathway

被引:57
作者
Jiang, Yang [1 ]
Zhou, Jinpeng [1 ]
Luo, Peng [1 ]
Gao, Huiling [2 ]
Ma, Yanju [3 ]
Chen, Yin-Sheng [4 ]
Li, Long [1 ]
Zou, Dan [5 ]
Zhang, Ye [5 ]
Jing, Zhitao [1 ]
机构
[1] China Med Univ, Hosp 1, Dept Neurosurg, 155 North Nanjing St, Shenyang 110001, Liaoning, Peoples R China
[2] Northeastern Univ, Coll Life & Hlth Sci, Shenyang, Liaoning, Peoples R China
[3] China Med Univ, Dept Med Oncol, Canc Hosp, Shenyang 110042, Liaoning, Peoples R China
[4] SunYat Sen Univ, Dept Neurosurg Neurooncol, Canc Ctr, State Key Lab Oncol South China,Collaborat Innova, Guangzhou 510060, Guangdong, Peoples R China
[5] China Med Univ, Hosp 1, Lab 1, Canc Inst, 155 North Nanjing St, Shenyang 110001, Liaoning, Peoples R China
基金
中国国家自然科学基金;
关键词
Glioma; Glioma stem cells; Prosaposin; Proliferation; Tumorigenesis; STEM-CELLS; CANCER; TLR4; INFLAMMATION; SECRETION; GENE; TRANSFORMATION; METASTASIS; DEFICIENCY; EXPRESSION;
D O I
10.1016/j.ebiom.2018.10.053
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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-kappa B 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/kappa B signaling pathway and may be an important target for glioma treatment. Interpretation: The findings of this study suggest that PSAP can promote glioma cell proliferation via the TLR4/NF-kappa B signaling pathway and may be an important target for glioma treatment. (C) 2018 Published by Elsevier B.V.
引用
收藏
页码:78 / 90
页数:13
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