Prosaposin is a biomarker of mesenchymal glioblastoma and regulates mesenchymal transition through the TGF‐β1/Smad signaling pathway

Autor: Jinpeng Zhou, Long Li, Yang Jiang, Haiying Zhang, Ye Zhang, Peng Luo, Yin-Sheng Chen, Yanju Ma, Dianqi Hou, Zhitao Jing, Dan Zou, Huiling Gao
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Epithelial-Mesenchymal Transition
Mesenchymal Glioblastoma
Mice
Nude

Smad Proteins
SMAD
Biology
urologic and male genital diseases
Saposins
Pathology and Forensic Medicine
Transforming Growth Factor beta1
03 medical and health sciences
0302 clinical medicine
Cell Movement
Neurotrophic factors
Cell Line
Tumor

Glioma
Biomarkers
Tumor

Tumor Cells
Cultured

medicine
Animals
Humans
Neoplasm Invasiveness
Phosphorylation
Prosaposin
Mice
Inbred BALB C

Brain Neoplasms
urogenital system
Mesenchymal stem cell
Middle Aged
medicine.disease
female genital diseases and pregnancy complications
nervous system diseases
030104 developmental biology
030220 oncology & carcinogenesis
Neoplastic Stem Cells
Cancer research
Female
Stem cell
Glioblastoma
Signal Transduction
Transforming growth factor
Zdroj: The Journal of Pathology. 249:26-38
ISSN: 1096-9896
0022-3417
DOI: 10.1002/path.5278
Popis: Mesenchymal glioblastoma (GBM) is the most aggressive subtype of GBM. Our previous study found that neurotrophic factor prosaposin (PSAP) is highly expressed and secreted in glioma and can promote the growth of glioma. The role of PSAP in mesenchymal GBM is still unclear. In this study, bioinformatic analysis, western blotting and RT-qPCR were used to detect the expression of PSAP in different GBM subtypes. Human glioma cell lines and patient-derived glioma stem cells were studied in vitro and in vivo, revealing that mesenchymal GBM expressed and secreted the highest level of PSAP among four subtypes of GBM, and PSAP could promote GBM invasion and epithelial-mesenchymal transition (EMT)-like processes in vivo and in vitro. Bioinformatic analysis and western blotting showed that PSAP mainly played a regulatory role in GBM invasion and EMT-like processes via the TGF-β1/Smad signaling pathway. In conclusion, the overexpression and secretion of PSAP may be an important factor causing the high invasiveness of mesenchymal GBM. PSAP is therefore a potential target for the treatment of mesenchymal GBM. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Databáze: OpenAIRE