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A gastrin-releasing peptide receptor antagonist stimulates Neuro2a neuroblastoma cell growth: Prevention by a histone deacetylase inhibitor

Authors

  • Ana Lucia Abujamra,

    1. Cancer Research Laboratory, Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2350, 90035-003 Porto Alegre, RS, Brazil
    2. Children's Cancer Institute and Pediatric Oncology Unit, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2350, 90035-003 Porto Alegre, RS, Brazil
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    • Ana Lucia Abujamra and Viviane R Almeida contributed equally to this article.

  • Viviane R. Almeida,

    1. Cancer Research Laboratory, Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2350, 90035-003 Porto Alegre, RS, Brazil
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    • Ana Lucia Abujamra and Viviane R Almeida contributed equally to this article.

  • Algemir L. Brunetto,

    1. Cancer Research Laboratory, Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2350, 90035-003 Porto Alegre, RS, Brazil
    2. Children's Cancer Institute and Pediatric Oncology Unit, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2350, 90035-003 Porto Alegre, RS, Brazil
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  • Gilberto Schwartsmann,

    1. Cancer Research Laboratory, Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2350, 90035-003 Porto Alegre, RS, Brazil
    2. Department of Internal Medicine, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil
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  • Rafael Roesler

    Corresponding author
    1. Cancer Research Laboratory, Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2350, 90035-003 Porto Alegre, RS, Brazil
    2. Children's Cancer Institute and Pediatric Oncology Unit, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2350, 90035-003 Porto Alegre, RS, Brazil
    3. Cellular and Molecular Neuropharmacology Research Group, Department of Pharmacology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500 (ICBS/Campus Centro/UFRGS), 90046-900 Porto Alegre, RS, Brazil
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Department of Pharmacology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500 (ICBS/Campus Centro/UFRGS), 90046-900 Porto Alegre, RS, Brazil. Tel./fax: +55 51 3308 3183. E-mail addresses: rroesler@terra.com.br

Abstract

Gastrin-releasing peptide (GRP) acts as an autocrine growth factor for neuroblastoma and other types of cancer, and its cell-surface receptor, GRPR, is overexpressed in advanced-stage human neuroblastoma. GRPR knockdown and GRPR antagonism inhibit the growth of experimental neuroblastoma. Here we show that a GRPR antagonist promotes rather than inhibits the growth of neuroblastoma cells. The GRPR antagonist, RC-3095, at 0.1 nM inhibited, whereas at 100 nM stimulated proliferation of Neuro2a murine neuroblastoma cells in vitro. The stimulatory effects were prevented by the histone deacetylase inhibitor (HDACi), sodium butyrate (NaB). Expression of GRPR mRNA in Neuro2a cells was analyzed by RT-PCR. These findings provide evidence that a GRPR antagonist can stimulate the growth of cancer cells, and suggest that GRPR might interact with epigenetic mechanisms in regulating neuroblastoma cell growth.

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