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Table of Contents
Vol. 79, No. 5-6, 2010
Issue release date: April 2011
Section title: Clinical Translational Research
Oncology 2010;79:430–439
(DOI:10.1159/000326564)

BDNF/TrkB Content and Interaction with Gastrin-Releasing Peptide Receptor Blockade in Colorectal Cancer

Brunetto de Farias C.a, m, n · Rosemberg D.B.d · Heinen T.E.a · Koehler-Santos P.b · Abujamra A.L.a, m, n · Kapczinski F.c, f, n · Brunetto A.L.a, g, m, n · Ashton-Prolla P.b, j · Meurer L.k · Reis Bogo M.n, o · Damin D.C.h, l · Schwartsmann G.a, i, n · Roesler R.a, e, n
Laboratories of aCancer Research, bGenomic Medicine and cMolecular Psychiatry, University Hospital Research Center (CPE-HCPA), dDepartment of Biochemistry, and eLaboratory of Molecular Neuropharmacology, Department of Pharmacology, Institute of Basic Health Sciences, Departments of fPsychiatry, gPediatrics, hSurgery and iInternal Medicine, School of Medicine, jDepartment of Genetics, Institute of Biosciences, and kDepartment of Pathology and lDivision of Coloproctology, University Hospital, Federal University of Rio Grande do Sul, mChildren’s Cancer Institute (ICI-RS), nNational Institute for Translational Medicine (INCT-TM), and oLaboratory of Genomic and Molecular Biology, School of Biosciences, Pontifical Catholic University, Porto Alegre, Brazil

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Article / Publication Details

First-Page Preview
Abstract of Clinical Translational Research

Received: October 11, 2010
Accepted: January 04, 2011
Published online: April 08, 2011
Issue release date: April 2011

Number of Print Pages: 10
Number of Figures: 5
Number of Tables: 1

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: http://www.karger.com/OCL

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.

© 2011 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Clinical Translational Research

Received: October 11, 2010
Accepted: January 04, 2011
Published online: April 08, 2011
Issue release date: April 2011

Number of Print Pages: 10
Number of Figures: 5
Number of Tables: 1

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: http://www.karger.com/OCL


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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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