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

被引：55

作者：

de Farias, Caroline Brunetto ^{[1
,13
,14
]}

Rosemberg, Denis Broock ^{[5
]}

Heinen, Tiago Elias ^{[1
]}

Koehler-Santos, Patricia ^{[2
]}

Abujamra, Ana Lucia ^{[1
,13
,14
]}

Kapczinski, Flavio ^{[3
,6
,14
]}

Brunetto, Algemir Lunardi ^{[1
,7
,13
,14
]}

Ashton-Prolla, Patricia ^{[2
,10
]}

Meurer, Luise ^{[11
]}

Bogo, Mauricio Reis ^{[14
,15
]}

Damin, Daniel C. ^{[8
,12
]}

Schwartsmann, Gilberto ^{[1
,9
,14
]}

Roesler, Rafael ^{[1
,4
,14
]}

机构：

[1] Univ Fed Rio Grande do Sul, Univ Hosp Res Ctr CPE HCPA, Canc Res Lab, BR-90050070 Porto Alegre, RS, Brazil

[2] Univ Fed Rio Grande do Sul, Univ Hosp Res Ctr CPE HCPA, Lab Genom Med, BR-90050070 Porto Alegre, RS, Brazil

[3] Univ Fed Rio Grande do Sul, Univ Hosp Res Ctr CPE HCPA, Lab Mol Psychiat, BR-90050070 Porto Alegre, RS, Brazil

[4] Univ Fed Rio Grande do Sul, Inst Basic Hlth Sci, Dept Pharmacol, ICBS,Lab Mol Neuropharmacol, BR-90050070 Porto Alegre, RS, Brazil

[5] Univ Fed Rio Grande do Sul, Dept Biochem, BR-90050070 Porto Alegre, RS, Brazil

[6] Univ Fed Rio Grande do Sul, Dept Psychiat, BR-90050070 Porto Alegre, RS, Brazil

[7] Univ Fed Rio Grande do Sul, Dept Pediat, BR-90050070 Porto Alegre, RS, Brazil

[8] Univ Fed Rio Grande do Sul, Dept Surg, BR-90050070 Porto Alegre, RS, Brazil

[9] Univ Fed Rio Grande do Sul, Sch Med, Dept Internal Med, BR-90050070 Porto Alegre, RS, Brazil

[10] Univ Fed Rio Grande do Sul, Inst Biosci, Dept Genet, BR-90050070 Porto Alegre, RS, Brazil

[11] Univ Fed Rio Grande do Sul, Univ Hosp, Dept Pathol, BR-90050070 Porto Alegre, RS, Brazil

[12] Univ Fed Rio Grande do Sul, Univ Hosp, Div Coloproctol, BR-90050070 Porto Alegre, RS, Brazil

[13] Childrens Canc Inst ICI RS, Porto Alegre, RS, Brazil

[14] Natl Inst Translat Med INCT TM, Porto Alegre, RS, Brazil

[15] Pontifical Catholic Univ, Sch Biosci, Lab Genom & Mol Biol, Porto Alegre, RS, Brazil

来源：

ONCOLOGY | 2010年 / 79卷 / 5-6期

关键词：

Brain-derived neurotrophic factor; TrkB; Gastrin-releasing peptide receptor; Epidermal growth factor receptor; HT-29; cells; Colorectal cancer; GROWTH-FACTOR RECEPTOR; CELL CARCINOMA-CELLS; ANTAGONIST RC-3095; NEUROTROPHIC FACTOR; ANTICANCER THERAPY; BDNF; TRKB; PROLIFERATION; ACTIVATION; EXPRESSION;

D O I：

10.1159/000326564

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 non-neoplastic 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. Copyright (C) 2011 S. Karger AG, Basel

引用

页码：430 / 439

页数：10

共 40 条

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