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: Caroline Brunetto de Farias, Denis Broock Rosemberg, Tiago Elias Heinen, Patricia Koehler-Santos, Ana Lucia Abujamra, Flávio Kapczinski, Algemir Lunardi Brunetto, Patricia Ashton-Prolla, Luise Meurer, Maurício Reis Bogo, Daniel C Damin, Gilberto Schwartsmann, Rafael Roesler
• Journal: Oncology (Oncology) Vol. 79 Issue 5-6 Pg. 430-9 ( 2010) ISSN: 1423-0232 [Electronic] Switzerland
• PMID: 21474968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 S. Karger AG, Basel.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Brain-Derived Neurotrophic Factor
• RNA, Messenger
• Receptors, Bombesin
• Recombinant Proteins
• ErbB Receptors
• Receptor, trkB
• Cetuximab

Topics

• Antibodies, Monoclonal (immunology, pharmacology)
• Antibodies, Monoclonal, Humanized
• Brain-Derived Neurotrophic Factor (genetics, metabolism)
• Cell Line, Tumor
• Cell Proliferation
• Cetuximab
• Colorectal Neoplasms (metabolism)
• Enzyme-Linked Immunosorbent Assay
• ErbB Receptors (antagonists & inhibitors, immunology, metabolism)
• Gene Expression
• HT29 Cells
• Humans
• RNA, Messenger (analysis)
• Receptor, trkB (genetics, metabolism)
• Receptors, Bombesin (antagonists & inhibitors)
• Recombinant Proteins (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• Tumor Cells, Cultured