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Exendin-4 induces cell adhesion and differentiation and counteracts the invasive potential of human neuroblastoma cells

Periodical: PLoS One ISBN: 1932-6203 (Electronic) 1932-6203 (Linking)  Number: 8  Date: 2013/08/31  Language: eng  Pages: e71716

Authors:Luciani, P., Deledda, C., Benvenuti, S., Squecco, R., Cellai, I., Fibbi, B., Marone, I. M., Giuliani, C., Modi, G., Francini, F., Vannelli, G. B., Peri, A.
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Abstract
Exendin-4 is a molecule currently used, in its synthetic form exenatide, for the treatment of type 2 diabetes mellitus. Exendin-4 binds and activates the Glucagon-Like Peptide-1 Receptor (GLP-1R), thus inducing insulin release. More recently, additional biological properties have been associated to molecules that belong to the GLP-1 family. For instance, Peptide YY and Vasoactive Intestinal Peptide have been found to affect cell adhesion and migration and our previous data have shown a considerable actin cytoskeleton rearrangement after exendin-4 treatment. However, no data are currently available on the effects of exendin-4 on tumor cell motility. The aim of this study was to investigate the effects of this molecule on cell adhesion, differentiation and migration in two neuroblastoma cell lines, SH-SY5Y and SK-N-AS. We first demonstrated, by Extra Cellular Matrix cell adhesion arrays, that exendin-4 increased cell adhesion, in particular on a vitronectin substrate. Subsequently, we found that this molecule induced a more differentiated phenotype, as assessed by i) the evaluation of neurite-like protrusions in 3D cell cultures, ii) the analysis of the expression of neuronal markers and iii) electrophysiological studies. Furthermore, we demonstrated that exendin-4 reduced cell migration and counteracted anchorage-independent growth in neuroblastoma cells. Overall, these data indicate for the first time that exendin-4 may have anti-tumoral properties.
Keywords
Adult, Cell Count, Dermis/cytology, Dimethylpolysiloxanes/pharmacology, Fibroblasts/cytology/drug effects, Hair Follicle/ drug effects/ growth & development, Humans, Hydrogel/ pharmacology, Keratinocytes/cytology/drug effects, Mechanical Phenomena/drug effects, Polyethylene Glycols, Tissue Culture Techniques, Tissue Engineering/ methods

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