title: Exendin-4 induces cell adhesion and differentiation and counteracts the invasive potential of human neuroblastoma cells.
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.
authors.affiliation: Endocrine Unit, "Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies" (DENOThe), Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Luciani
authors.forename: Cristiana
authors.initials: C
authors.lastname: Deledda
authors.forename: Susanna
authors.initials: S
authors.lastname: Benvenuti
authors.forename: Roberta
authors.initials: R
authors.lastname: Squecco
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cellai
authors.forename: Benedetta
authors.initials: B
authors.lastname: Fibbi
authors.forename: Ilaria Maddalena
authors.initials: IM
authors.lastname: Marone
authors.forename: Corinna
authors.initials: C
authors.lastname: Giuliani
authors.forename: Giulia
authors.initials: G
authors.lastname: Modi
authors.forename: Fabio
authors.initials: F
authors.lastname: Francini
authors.forename: Gabriella Barbara
authors.initials: GB
authors.lastname: Vannelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Peri
mesh_terms: D015220:Calcium Channels / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000077270:Exenatide; D015870:Gene Expression / Q000187:drug effects; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009361:Neoplasm Invasiveness; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D018027:Receptors, Glucagon / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016708:Synaptophysin / Q000235:genetics; D014688:Venoms / Q000494:pharmacology*; D019096:Vitronectin / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics
chemical_list: D015220:Calcium Channels; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; D010455:Peptides; D018027:Receptors, Glucagon; D055293:Receptors, Urokinase Plasminogen Activator; D016708:Synaptophysin; D014688:Venoms; D019096:Vitronectin; D016875:tau Proteins; D000077270:Exenatide