title: BDNF/TrkB content and interaction with gastrin-releasing peptide receptor blockade in colorectal cancer.
abstract: OBJECTIVE
  Neurotrophin and neuropeptide pathways are emerging targets in cancer. Here we show that brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, are present in colorectal cancer and that BDNF levels are increased in tumors compared to nontumor tissue. In addition, we investigate the role of BDNF in influencing the response of colorectal cancer cells to inhibition of gastrin-releasing peptide receptors (GRPR).
  
  
  METHODS
  Fresh-frozen sporadic colorectal adenocarcinoma specimens and adjacent nonneoplastic tissue from 30 patients, as well as paraffin-embedded colorectal cancer samples from 21 patients, were used in this study. Cell proliferation and mRNA and protein levels were examined in HT-29 or SW620 cells treated with a GRPR antagonist, human recombinant BDNF (hrBDNF), a Trk antagonist K252a, or cetuximab.
  
  
  RESULTS
  Expression of BDNF and TrkB was detected in tumor samples and cell lines. BDNF levels were higher in tumor samples compared to nonneoplastic tissue. BDNF expression and secretion were increased by GRPR blockade in HT-29 cells through a mechanism dependent on epidermal growth factor receptors. Treatment with hrBDNF prevented the effect of GRPR blockade on cell proliferation, whereas a Trk inhibitor reduced proliferation.
  
  
  CONCLUSIONS
  BDNF and TrkB are present in colorectal cancer and might contribute to resistance to GRPR antagonists.
authors.affiliation: Laboratorie of Cancer Research, University Hospital Research Center (CPE-HCPA), Porto Alegre, Brazil.
authors.forename: Caroline
authors.initials: C
authors.lastname: Brunetto de Farias
authors.forename: Denis Broock
authors.initials: DB
authors.lastname: Rosemberg
authors.forename: Tiago Elias
authors.initials: TE
authors.lastname: Heinen
authors.forename: Patricia
authors.initials: P
authors.lastname: Koehler-Santos
authors.forename: Ana Lucia
authors.initials: AL
authors.lastname: Abujamra
authors.forename: Flávio
authors.initials: F
authors.lastname: Kapczinski
authors.forename: Algemir Lunardi
authors.initials: AL
authors.lastname: Brunetto
authors.forename: Patricia
authors.initials: P
authors.lastname: Ashton-Prolla
authors.forename: Luise
authors.initials: L
authors.lastname: Meurer
authors.forename: Maurício
authors.initials: M
authors.lastname: Reis Bogo
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Damin
authors.forename: Gilberto
authors.initials: G
authors.lastname: Schwartsmann
authors.forename: Rafael
authors.initials: R
authors.lastname: Roesler
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D019073:HT29 Cells; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D018004:Receptors, Bombesin; D011994:Recombinant Proteins; D066246:ErbB Receptors; D020813:Receptor, trkB; D000068818:Cetuximab