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Effects of the vasoactive intestinal peptide (VIP) and related peptides on glioblastoma cell growth in vitro

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Abstract

The growth rate of numerous cancer cell lines is regulated in part by actions of neuropeptides of the vasoactive intestinal peptide (VIP) family, which also includes pituitary adenylate cyclase-activating peptide (PACAP), glucagon, and peptide histidine/isoleucine (PHI). The aim of this work was to investigate the effect of these peptides on the growth of the rat glioblastoma cell line C6 in vitro. We also sought to determine which binding sites were correlated with the effects observed. Proliferation studies performed by means of a CyQuant™ assay showed that VIP and PACAP strongly stimulated C6 cell proliferation at most of the concentrations tested, whereas PHI increased cell proliferation only when associated with VIP. Two growth hormone-releasing factor (GRF) derivatives and the VIP antagonist hybrid peptide neurotensin-VIP were able to inhibit VIP-induced cell growth stimulation, even at very low concentrations. Binding experiments carried out on intact cultured C6 cells, using 125I-labeled VIP and PACAP as tracers, revealed that the effects of the peptides on cell growth were correlated with the expression on C6 cells of polyvalent high-affinity VIP-PACAP binding sites and of a second subtype corresponding to very high-affinity VIP-selective binding species. The latter subtype, which interacted poorly with PACAP with a 10,000-fold lower affinity than VIP, might mediate the antagonist effects of neurotensin-VIP and of both GRF derivatives on VIP-induced cell growth stimulation.

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Authors and Affiliations

  1. Laboratoire de Biologie des Interactions Cellulaires, CNRS UMR 6558, Faculté de Sciences, Université de Poitiers, 86022, Poitiers, France

    Christine Dufes, Céline Alleaume, Alicia Montoni & Jean-Marc Muller

  2. Laboratoire de Pharmacie Galénique et Biopharmacie, Equipe Émergente Médicaments Anti-infectieux et Barrière Hématoencéphalique, Faculté de Médecine et Pharmacie, Université de Poitiers, 86000, Poitiers, France

    Jean-Christophe Olivier

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  1. Christine Dufes
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  2. Céline Alleaume
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  3. Alicia Montoni
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  4. Jean-Christophe Olivier
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  5. Jean-Marc Muller
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Correspondence to Jean-Marc Muller.

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Dufes, C., Alleaume, C., Montoni, A. et al. Effects of the vasoactive intestinal peptide (VIP) and related peptides on glioblastoma cell growth in vitro. J Mol Neurosci 21, 91–102 (2003). https://doi.org/10.1385/JMN:21:2:91

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  • DOI: https://doi.org/10.1385/JMN:21:2:91

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