title: BDNF mediated TrkB activation contributes to the EMT progression and the poor prognosis in human salivary adenoid cystic carcinoma.
abstract: BACKGROUND
  The aim of the present study was to investigate whether the expression of Brain-Derived Neurotrophic Factor (BDNF) and its receptor Tropomyosin-related kinase B (TrkB) is correlated with the clinical progression of salivary adenoid cystic carcinoma (SACC) and whether the BDNF/TrkB axis is associated with the induction of epithelial-mesenchymal transition (EMT) in SACC cells.
  
  
  METHODS
  The expression of BDNF, TrkB, and E-cadherin (an EMT biomarker) in 76 primary SACC specimens and 20 normal salivary gland tissues was analyzed by immunohistochemistry. Additionally, the expression of BDNF, TrkB, and E-cadherin in SACC cell lines (SACC-83 and SACC-LM) was analyzed by RT-PCR and Western blotting. The biological role of the BDNF/TrkB axis in the EMT progression of SACC was evaluated after treatment with increased levels of BDNF and by inhibiting TrkB activity in SACC-83 cell line. The progression of SACC cells through EMT was assessed by RT-PCR, Western blotting, photography, migration and invasion assays.
  
  
  RESULTS
  Elevated expression of TrkB (92.1%) and BDNF (89.5%), and downregulated expression of E-cadherin (47.4%) was found in SACC specimens, which was significantly correlated with the invasion and metastasis in SACC (P<0.05). The high expression of TrkB and the low expression of E-cadherin was significantly correlated with the poor prognosis of SACC patients (P<0.05). The expression of TrkB was inversely correlated with the expression of E-cadherin in both SACC cases and cell lines (P<0.05). Increasing BDNF levels after treatment with exogenous recombinant human BDNF (rhBDNF) at 100 ng/ml significantly promoted the activation of TrKB and the progression of EMT in SACC cells. While obstruction of TrkB by its inhibitor, k252a (100 nM), significantly inhibited the EMT progression of SACC cells.
  
  
  CONCLUSIONS
  These results suggest that BDNF-mediated TrkB activation contributes to the EMT progression and the poor prognosis in SACC. The present study demonstrated that the BDNF/TrkB axis promotes the migration and invasion of SACC cells via EMT in vitro. Targeting the inactivation of the BDNF/TrkB axis may be a potential strategy for the treatment of SACC.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China; No. 150 Hospital of PLA, Luoyang 471031, China.
authors.forename: Weixi
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Shan
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Baolei
authors.initials: B
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Zihui
authors.initials: Z
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: yangxinjie@fmmu.edu.cn.
authors.forename: Xinjie
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: leidelin@fmmu.edu.cn.
authors.forename: Delin
authors.initials: D
authors.lastname: Lei
mesh_terms: D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D015820:Cadherins / Q000378:metabolism; D003528:Carcinoma, Adenoid Cystic / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D017931:DNA Primers; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020813:Receptor, trkB; D012468:Salivary Gland Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015820:Cadherins; D017931:DNA Primers; D008562:Membrane Glycoproteins; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB; C000591259:tropomyosin-related kinase-B, human
keywords: BDNF; EMT; Salivary adenoid cystic carcinoma; TrkB