BDNF/TrkB在唾液腺腺样囊性癌上皮-间质转化过程中的表达及意义

中国口腔颌面外科杂志 ›› 2015, Vol. 13 ›› Issue (3): 211-215.

BDNF/TrkB在唾液腺腺样囊性癌上皮-间质转化过程中的表达及意义

胡志强^{1, 2}, 杨新杰¹, 王维玺^{1, 3}, 贾森¹, 吴宝磊¹, 雷德林¹

1.第四军医大学口腔医院口腔颌面外科,军事口腔医学国家重点实验室,陕西西安 710032;
2.解放军113医院,浙江宁波 315040;
3.解放军150医院,河南洛阳 471031

收稿日期:2014-10-13 修回日期:2015-01-05 出版日期:2015-05-20 发布日期:2015-06-18
通讯作者: 雷德林,Tel：029-84776105,E-mail：leidelin@fmmu.edu.cn
作者简介:胡志强（1982- ）,男,硕士研究生,E-mail：huzq8255@126.com
基金资助:
国家自然科学基金（81302352,81372901）

Expression of BDNF/TrkB in the progress of epithelial-mesenchymal transition in salivary adenoid cystic carcinoma

HU Zhi-qiang^{1, 2}, YANG Xin-jie¹, WANG Wei-xi^{1, 3}, JIA Sen¹, WU Bao-lei¹, LEI De-lin¹

1.State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Forth Military Medical University. Xi’an 710032, Shaanxi Province;
2.No.113 Hospital of PLA. Ningbo 315040, Zhejiang Province;
3.No.150 Hospital of PLA. Luoyang 471031, Henan Province, China

Received:2014-10-13 Revised:2015-01-05 Online:2015-05-20 Published:2015-06-18
Supported by:
Supported by National Natural Science Foundation of China (81302352, 81372901)

摘要/Abstract

摘要： 目的研究BDNF、TrkB和E-cadherin在唾液腺腺样囊性癌（SACC）细胞系中的表达,初步探讨BDNF、TrkB和E-cadherin与SACC高转移性及神经侵袭性之间的关系。方法以SACC高、低转移细胞系SACC-LM和SACC-83为研究对象,利用实时荧光定量 PCR和Western 免疫印迹技术检测BDNF、TrkB和E-cadherin在其中的表达差异;在SACC-83细胞系中加入外源性BDNF因子、TrkB抑制剂k252a,分析BDNF/TrkB通路在SACC侵袭转移过程中的生物学作用;利用实时荧光定量 PCR、Western 免疫印迹、细胞形态观察、细胞迁徙和侵袭实验评估SACC细胞上皮-间质转化（EMT）进程。应用SPSS17.0软件包对数据进行统计学处理。结果 BDNF 和TrkB在SACC-LM中的表达高于SACC- 83,E-cadherin在SACC-LM中的表达低于SACC- 83;外源性BDNF刺激能有效诱导TrkB的激活和表达,降低E-cadherin的表达,提高N-cadherin的表达,使细胞形态呈长梭形改变,促进SACC-83细胞的迁徙、侵袭能力;而TrkB受体抑制剂k252a可有效抑制BDNF的各种作用,降低SACC-83细胞形态变化和迁徙、侵袭能力。结论 BDNF/TrkB信号通路通过介导SACC的EMT过程,促进SACC的迁徙、侵袭能力。

关键词: BDNF, TrkB, E-cadherin, 唾液腺腺样囊性癌, 上皮-间质转化

Abstract: PURPOSE: To investigate the expression of BDNF,TrkB and E-cadherin in salivary adenoid cystic carcinoma (SACC) and study their role in metastasis and nerve invasion. METHODS: The high and low metastatic SACC cell lines (SACC-LM, SACC-83) were analyzed by real-time PCR and Western blot to determine the expression of BDNF, TrkB and E-cadherin. To observe the BDNF/TrkB pathway in the metastasis process of SACC, the SACC-83 cells were treated by exogenous BDNF and/or TrkB inhibitor k252a, respectively. Meanwhile, the epithelial mesenchymal transition (EMT) of SACC-83 cells were evaluated by real-time PCR, Western blot, morphology observation, cell migration and invasion analysis. SPSS 17.0 software package was employed to analyze the data statistically. RESULTS: The expression of BDNF and TrkB in SACC-LM cells were higher than SACC-83 cells whereas the E-cadherin was down regulated. Exogenous BDNF could activate TrkB, inhibit E-cadherin and promote N-cadherin expression in SACC-83 cells. The morphology of SACC-83 cells stimulated by BDNF was also elongated and migration and invasion capabilities were improved. When TrkB was inhibited by k252a, the BDNF effects were inhibited including the suppressing of SACC-83 morphology alteration, migration and invasion capabilities. CONCLUSIONS: BDNF/TrkB pathway can promote the migration and invasion capabilities of SACC cells by mediating its EMT progression.

Key words: BDNF, TrKB, E-cadherin, Salivary adenoid cystic carcinoma, Tumor invasion, Epithelial-mesenchymal transition, EMT

中图分类号:

R739.87

胡志强, 杨新杰, 王维玺, 贾森, 吴宝磊, 雷德林. BDNF/TrkB在唾液腺腺样囊性癌上皮-间质转化过程中的表达及意义[J]. 中国口腔颌面外科杂志, 2015, 13(3): 211-215.

HU Zhi-qiang, YANG Xin-jie, WANG Wei-xi, JIA Sen, WU Bao-lei, LEI De-lin. Expression of BDNF/TrkB in the progress of epithelial-mesenchymal transition in salivary adenoid cystic carcinoma[J]. China J Oral Maxillofac Surg, 2015, 13(3): 211-215.

参考文献

[1] Laurie SA, Ho AL, Fury MG, et al. Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: a systematic review[J]. Lancet Oncol, 2011, 12(8): 815-824.
[2] 苏立新, 张陈平, 胡永杰, 等. BDNF 对唾液腺腺样囊性癌细胞株抗失巢凋亡能力和转移的影响[J]. 中国口腔颌面外科杂志, 2007, 5(3): 207-210.
[3] Ellington CL, Goodman M, Kono SA, et al. Adenoid cystic carcinoma of the head and neck: incidence and survival trends based on 1973-2007 Surveillance, Epidemiology, and End Results data[J]. Cancer, 2012, 118(18): 4444-4451.
[4] 吕春堂, 周中华. 涎腺腺样囊性癌生物学特性与生物治疗[J]. 口腔颌面外科杂志, 2009, 19(3): 153-158.
[5] 罗荣城, 尤长宣. 肿瘤生物治疗新进展[J]. 中国新药杂志, 2005, 14(2): 143-146.
[6] Huang YT, Lai PC, Wu CC, et al. BDNF mediated TrkB activation is a survival signal for transitional cell carcinoma cells[J]. Int J Oncol, 2010, 36(6): 1469-1476.
[7] Au CW, Siu MK, Liao X, et al. Tyrosine kinase B receptor and BDNF expression in ovarian cancers effect on cell migration, angiogenesis and clinical outcome [J]. Cancer Letters, 2009, 281(2): 151-161.
[8] Bao W, Qiu H, Yang T, et al. Upregulation of TrkB promotes epithelial-mesenchymal transition and anoikis resistance in endometrial carcinoma [J]. PloS one, 2013, 8(7): e70616.
[9] Kupferman ME, Jiffar T, El-Naggar A, et al. TrkB induces EMT and has a key role in invasion of head and neck squamous cell carcinoma [J]. Oncogene, 2010, 29(14): 2047-2059.
[10] Odate S, Nakamura K, Onishi H, et al. TrkB/BDNF signaling pathway is a potential therapeutic target for pulmonary large cell neuroendocrine carcinoma [J]. Lung Cancer, 2013, 79(3): 205-214.
[11] Okamura K, Harada T, Wang S, et al. Expression of TrkB and BDNF is associated with poor prognosis in non-small cell lung cancer [J]. Lung cancer, 2012, 78(1): 100-106.
[12] Lessmann V, Gottmann K, Malcangio M. Neurotrophin secretion：current facts and future prospects [J]. Prog Neurobiol, 2003, 69(5): 34l-374.
[13] Guo D, Hou X, Zhang H, et al. More expressions of BDNF and TrkB in multiple hepatocellular carcinoma and anti-BDNF or K252a induced apoptosis, supressed invasion of HepG2 and HCCLM3 cells [J]. J Exp Clin Cancer Res, 2011, 30: 97.
[14] 苏立新, 张陈平, 胡永杰, 等. BDNF和TrkB在唾液腺腺样囊性癌中的表达及意义 [J]. 中国口腔颌面外科杂志, 2006, 4(5): 330-335.
[15] 王维玺, 杨新杰, 贾森, 等. BDNF、TrkB和E-cadherin在唾液腺腺样囊性癌中的表达及意义 [J]. 中国口腔颌面外科杂志, 2014, 12(4): 289-294.