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. 2015 Jul;10(1):223-227.
doi: 10.3892/ol.2015.3181. Epub 2015 May 6.

Mature brain-derived neurotrophic factor and its receptor TrkB are upregulated in human glioma tissues

Jing Xiong  1 , L I Zhou  2 , Yoon Lim  3 , Miao Yang  3 , Yu-Hong Zhu  1 , Zhi-Wei Li  1 , Deng-Li Fu  1 , Xin-Fu Zhou  4
Affiliations

Mature brain-derived neurotrophic factor and its receptor TrkB are upregulated in human glioma tissues

Jing Xiong et al. Oncol Lett. 2015 Jul.

Abstract

There are two forms of brain-derived neurotrophic factor (BDNF), precursor of BDNF (proBDNF) and mature BDNF, which each exert opposing effects through two different transmembrane receptor signaling systems, consisting of p75 neurotrophin receptor (p75NTR) and tyrosine receptor kinase B (TrkB). Previous studies have demonstrated that proBDNF promotes cell death and inhibits the growth and migration of C6 glioma cells through p75NTR in vitro, while mature BDNF has opposite effects on C6 glioma cells. It is hypothesized that mature BDNF is essential in the development of malignancy in gliomas. However, histological data obtained in previous studies were unable distinguish mature BDNF from proBDNF due to the lack of specific antibodies. The present study investigated the expression of mature BDNF using a specific sheep monoclonal anti-mature BDNF antibody in 42 human glioma tissues of different grades and 10 control tissues. The correlation between mature BDNF and TrkB was analyzed. Mature BDNF expression was significantly increased in high-grade gliomas, and was positively correlated with the malignancy of the tumor and TrkB receptor expression. The present data have demonstrated that increased levels of mature BDNF contribute markedly to the development of malignancy of human gliomas through the primary BDNF receptor TrkB.

Keywords: brain-derived neurotrophic factor; glioma; human; tyrosine receptor kinase B.

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Figures

Figure 1.
Figure 1.
Expression of mature BDNF in human glioma tissues at various grades of malignancy. (A-C) IHC for mature BDNF in (A) control tissue, (B) low-grade glioma tissue and (C) high-grade glioma tissue (scale bar, 25 µm). (D) IHC scores for mature BDNF immunostaining. (E) Detection of BDNF mRNA by reverse transcription-quantitative polymerase chain reaction. (F) Findings of the ELISA assay. **P<0.01 vs. control. BDNF, brain-derived neurotrophic factor; IHC, immunohistochemistry; DAB, 3,3′-diaminobenzidine.
Figure 2.
Figure 2.
Expression of TrkB in human glioma tissues at various grades of malignancy. (A-D) IHC for TrkB in (A) control tissues, (B) low-grade glioma tissues and (C) high-grade glioma tissues (scale bar, 25 µm). (D) IHC scores for TrkB immunostaining. (E) Detection of TrkB mRNA by reverse transcription-quantitative polymerase chain reaction. (F) Findings of the ELISA assay. **P<0.01, *P<0.05 vs. control. TrkB, tyrosine receptor kinase B; IHC, immunohistochemistry.
Figure 3.
Figure 3.
Correlation between mature BDNF and TrkB expression and glioma tumor grade. (A) Correlation between mature BDNF expression and the tumor grade. (B) Correlation between TrkB expression and tumor grade. (C) Correlation between the expression of mature BDNF and the expression of TrkB. BDNF, brain-derived neurotrophic factor; TrkB, tyrosine receptor kinase B.
See this image and copyright information in PMC

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