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

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...

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Published in:PloS one 2013-08, Vol.8 (8), p.e71716
Main Authors: Luciani, Paola, Deledda, Cristiana, Benvenuti, Susanna, Squecco, Roberta, Cellai, Ilaria, Fibbi, Benedetta, Marone, Ilaria Maddalena, Giuliani, Corinna, Modi, Giulia, Francini, Fabio, Vannelli, Gabriella Barbara, Peri, Alessandro
Format: Article
Language:English
Subjects:
Acids
Actin
Adhesion
Analysis
Biological properties
Biology
Calcium Channels - metabolism
Cancer therapies
Cell adhesion
Cell adhesion & migration
Cell Adhesion - drug effects
Cell adhesion molecules
Cell culture
Cell Culture Techniques
Cell differentiation
Cell Differentiation - drug effects
Cell growth
Cell Line, Tumor
Cell migration
Cell Movement - drug effects
Cell Survival - drug effects
Cells, Cultured
Chemokines
Cytoskeleton
Diabetes
Diabetes mellitus
Diabetes therapy
Differentiation (biology)
Education
Endocrinology
Gene Expression - drug effects
Glucagon
Glucagon-like peptide 1
Glucagon-Like Peptide-1 Receptor
Humans
Hypoglycemic Agents - pharmacology
Insulin
Intestine
Kinases
Medicine
Membrane Potentials - drug effects
Metastasis
Microtubule-Associated Proteins - genetics
Motility
Neoplasm Invasiveness
Nervous system
Neuroblastoma
Neuroblastoma - genetics
Neuroblastoma - metabolism
Neuroblastoma - pathology
Neuroblastoma cells
Peptides
Peptides - pharmacology
Physiology
Protein Binding - drug effects
Receptors, Glucagon - genetics
Receptors, Urokinase Plasminogen Activator - genetics
Reverse Transcriptase Polymerase Chain Reaction
Rodents
Studies
Substrates
Synaptophysin - genetics
tau Proteins - genetics
Thyroid cancer
Tumors
Type 2 diabetes
Vasoactive agents
Vasoactive intestinal peptide
Vasoactive intestinal peptides
Venoms - pharmacology
Vitronectin
Vitronectin - metabolism
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0071716