title: ProBDNF and its receptors are upregulated in glioma and inhibit the growth of glioma cells in vitro.
abstract: BACKGROUND
  High-grade glioma is incurable, with a short survival time and poor prognosis. The increased expression of p75 neurotrophin receptor (NTR) is a characteristic of high-grade glioma, but the potential significance of increased p75NTR in this tumor is not fully understood. Since p75NTR is the receptor for the precursor of brain-derived neurotrophic factor (proBDNF), it is suggested that proBDNF may have an impact on glioma.
  
  
  METHODS
  In this study we investigated the expression of proBDNF and its receptors p75NTR and sortilin in 52 cases of human glioma and 13 cases of controls by immunochemistry, quantitative real-time PCR, and Western blot methods. Using C6 glioma cells as a model, we investigated the roles of proBDNF on C6 glioma cell differentiation, growth, apoptosis, and migration in vitro.
  
  
  RESULTS
  We found that the expression levels of proBDNF, p75NTR, and sortilin were significantly increased in high-grade glioma and were positively correlated with the malignancy of the tumor. We also observed that tumors expressed proBDNF, p75NTR, and sortilin in the same cells with different subcellular distributions, suggesting an autocrine or paracrine loop. The ratio of proBDNF to mature BDNF was decreased in high-grade glioma tissues and was negatively correlated with tumor grade. Using C6 glioma cells as a model, we found that proBDNF increased apoptosis and differentiation and decreased cell growth and migration in vitro via p75NTR.
  
  
  CONCLUSIONS
  Our data indicate that proBDNF and its receptors are upregulated in high-grade glioma and might play an inhibitory effect on glioma.
authors.affiliation: Key Laboratory of Stem Cells and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, Yunnan Province, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xiong
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Miao
authors.initials: M
authors.lastname: Yang
authors.forename: Yoon
authors.initials: Y
authors.lastname: Lim
authors.forename: Yu-hong
authors.initials: YH
authors.lastname: Zhu
authors.forename: Deng-li
authors.initials: DL
authors.lastname: Fu
authors.forename: Zhi-wei
authors.initials: ZW
authors.lastname: Li
authors.forename: Jin-hua
authors.initials: JH
authors.lastname: Zhong
authors.forename: Zhi-cheng
authors.initials: ZC
authors.lastname: Xiao
authors.forename: Xin-Fu
authors.initials: XF
authors.lastname: Zhou
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000328:Adult; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020800:Receptor, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D014408:Biomarkers, Tumor; D019208:Brain-Derived Neurotrophic Factor; D011498:Protein Precursors; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D000099183:Sortilin; C426674:brain-derived neurotrophic factor precursor
keywords: brain-derived neurotrophic factor; glioma; human; p75NTR; proBDNF; sortilin