More expression of BDNF associates with lung squamous cell carcinoma and is critical to the proliferation and invasion of lung cancer cells.

Si-yang Zhang,Jian Gao,Lin-ping Hui,Xue-shan Qiu,Ze-shi Cui,Chun-yan Li

doi:10.1186/s12885-016-2218-0

Si-yang Zhang, Jian Gao + Show 4 more

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https://doi.org/10.1186/s12885-016-2218-0

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Journal: BMC cancer	Publication Date: Feb 29, 2016
Citations: 55	License type: cc-by

Affiliation: China Medical University

Abstract

BackgroundBrain-derived neurotrophic factor (BDNF) has been reported to promote tumorigenesis and progression in several human malignancies. The purpose of this study was to explore the function of BDNF in lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC).MethodsThe expression of BDNF was examined in 110 samples of lung SCC and ADC by immunohistochemistry. The protein level of BDNF was examined in 25 lung SCC or ADC samples and paired non-tumors by western blot. BDNF expression was also evaluated in human bronchial epithelial cells (HBE) and 4 lung cancer cell lines using western blot. Three BDNF mRNA variants containing exons IV, VI and IX were evaluated in HBE, two SCC (SK, LK2) and two ADC (A549, LTE) cell lines by RT-PCR. The expression and secretion of BDNF were also determined in cells using western blot and ELISA. Then the shRNA specific for BDNF was transfected into LK2 or A549 cells to further elucidate the BDNF knockdown on cell proliferation, apoptosis and invasion, which were confirmed by MTT, flow cytometry and transwell examinations.Results71.8 % (79 out of 110) of lung SCC and ADC samples were detected positive BDNF, and high expression of BDNF was significantly correlated with histological type and T stage. Compared with non-tumorous counterparts, BDNF was apparently overexpressed in SCC and ADC tissues. In cell studies, the extensive expression and secretion of BDNF were demonstrated in lung cancer cells compared with HBE cells. Interestingly, the expressions of BDNF mRNA variant IV and VI were identical in all cells examined. However, more expression of BDNF mRNA variant IX was found in SK and LK2 cells. The apoptotic cells were increased, and the cell proliferation and invasion were both attenuated once the expression of BDNF was inhibited. When retreated by rhBDNF, BDNF knockdown cells showed less apoptotic or more proliferative and invasive.ConclusionsOur data show that BDNF probably facilitates the tumorigenesis of lung SCC and ADC. The expression of BDNF mRNA variant IX is probably more helpful to the upregulation of BDNF in SCC, and intervening the production of BDNF could be a possible strategy to lung cancer therapy.

Highlights

Brain-derived neurotrophic factor (BDNF) has been reported to promote tumorigenesis and progression in several human malignancies
These findings indicated that BDNF/tropomyosin-related receptor kinase B (TrkB) signaling was closely associated with tumor progression [10], and it has emerged as a potential therapeutic target [11]
BDNF expression in specimens of lung squamous cell carcinoma (SCC) and ADC by Immunohistochemistry Weak expression of BDNF was shown in the cytoplasm of bronchial epithelial cells (Fig. 1a), and no expression was found in alveolar epithelium (Fig. 1d)

Summary

Introduction

Brain-derived neurotrophic factor (BDNF) has been reported to promote tumorigenesis and progression in several human malignancies. BDNF and TrkB have been reported to promote tumorigenesis and progression in several human malignancies such as neuroblastoma [3], breast [4], lung [5], prostate [6], and colon cancer [7]. Studies have shown that BDNF/TrkB signaling was involved in proliferative [8] or invasive properties [9]. These findings indicated that BDNF/TrkB signaling was closely associated with tumor progression [10], and it has emerged as a potential therapeutic target [11]

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