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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Calcium Channels / metabolism
-
Cell Adhesion / drug effects
-
Cell Culture Techniques
-
Cell Differentiation / drug effects*
-
Cell Line, Tumor
-
Cell Movement / drug effects*
-
Cell Survival / drug effects
-
Cells, Cultured
-
Exenatide
-
Gene Expression / drug effects
-
Glucagon-Like Peptide-1 Receptor
-
Humans
-
Hypoglycemic Agents / pharmacology
-
Membrane Potentials / drug effects
-
Microtubule-Associated Proteins / genetics
-
Neoplasm Invasiveness
-
Neuroblastoma / genetics
-
Neuroblastoma / metabolism
-
Neuroblastoma / pathology
-
Peptides / pharmacology*
-
Protein Binding / drug effects
-
Receptors, Glucagon / genetics
-
Receptors, Urokinase Plasminogen Activator / genetics
-
Reverse Transcriptase Polymerase Chain Reaction
-
Synaptophysin / genetics
-
Venoms / pharmacology*
-
Vitronectin / metabolism
-
tau Proteins / genetics
Substances
-
Calcium Channels
-
GLP1R protein, human
-
Glucagon-Like Peptide-1 Receptor
-
Hypoglycemic Agents
-
MAP2 protein, human
-
Microtubule-Associated Proteins
-
Peptides
-
Receptors, Glucagon
-
Receptors, Urokinase Plasminogen Activator
-
Synaptophysin
-
Venoms
-
Vitronectin
-
tau Proteins
-
Exenatide
Grants and funding
This study was supported by grants from Ente Cassa di Risparmio di Firenze, from the Regione Toscana “Bando Salute 2009” and from Ministero dell’Istruzione, dell’Università e della Ricerca (PRIN 2009 n. 2009YJTBAZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.