title: Brain-derived neurotrophic factor/tropomyosin-related kinase B pathway in gastric cancer.
abstract: BACKGROUND
  Brain-derived neutrophic factor (BDNF) is a member of the neutrophin family that is known to activate the high-affinity tropomyosin-related receptor kinase B (TrkB). This study aimed to clarify the clinical and biological significance of the BDNF/TrkB pathway in gastric cancer.
  
  
  METHODS
  We analysed BDNF and TrkB expression in gastric cancer samples by real-time reverse transcription PCR and immunohistochemistry. To investigate the biological role of BDNF/TrkB axis, recombinant human BDNF (rhBDNF) and the Trk antagonist K252a were used for in vitro and in vivo analysis.
  
  
  RESULTS
  The BDNF expression at the invasive front of primary tumours was significantly elevated compared with that in the tumour core and adjacent normal mucosa. Increased BDNF expression at the invasive front was significantly correlated with factors reflecting disease progression, and poor prognosis. Increased co-expression of the BDNF/TrkB axis was significantly correlated with poor prognosis. Gastric cancer cells expressed BDNF, and administration of rhBDNF promoted proliferation, migration, invasion, and inhibition of anoikis. These effects were generally inhibited by K252a. In an in vivo assay, BDNF(+)/TrkB(+) gastric cancer cells injected into nude mice established peritoneal dissemination, whereas K252a inhibited tumour growth.
  
  
  CONCLUSIONS
  The BDNF/TrkB pathway might be deeply involved in gastric cancer disease progression.
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu 514-8507, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okugawa
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: M
authors.initials: M
authors.lastname: Kawamura
authors.forename: A
authors.initials: A
authors.lastname: Kawamoto
authors.forename: J
authors.initials: J
authors.lastname: Hiro
authors.forename: S
authors.initials: S
authors.lastname: Saigusa
authors.forename: Y
authors.initials: Y
authors.lastname: Toiyama
authors.forename: M
authors.initials: M
authors.lastname: Ohi
authors.forename: K
authors.initials: K
authors.lastname: Uchida
authors.forename: Y
authors.initials: Y
authors.lastname: Mohri
authors.forename: M
authors.initials: M
authors.lastname: Kusunoki
mesh_terms: D000368:Aged; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D011379:Prognosis; D020813:Receptor, trkB / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB