title: VIP and PACAP analogs regulate therapeutic targets in high-risk neuroblastoma cells.
abstract: Neuroblastoma (NB) is a pediatric cancer. New therapies for high-risk NB aim to induce cell differentiation and to inhibit MYCN and ALK signaling in NB. The vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase-activating polypeptide (PACAP) are 2 related neuropeptides sharing common receptors. The level of VIP increases with NB differentiation. Here, the effects of VIP and PACAP analogs developed for therapeutic use were studied in MYCN-amplified NB SK-N-DZ and IMR-32 cells and in Kelly cells that in addition present the F1174L ALK mutation. As previously reported by our group in IMR-32 cells, VIP induced neuritogenesis in SK-N-DZ and Kelly cells and reduced MYCN expression in Kelly but not in SK-N-DZ cells. VIP decreased AKT activity in the ALK-mutated Kelly cells. These effects were PKA-dependent. IMR-32, SK-NDZ and Kelly cells expressed the genes encoding the 3 subtypes of VIP and PACAP receptors, VPAC1, VPAC2 and PAC1. In parallel to its effect on MYCN expression, VIP inhibited invasion in IMR-32 and Kelly cells. Among the 3 PACAP analogs tested, [Hyp(2)]PACAP-27 showed higher efficiency than VIP in Kelly cells. These results indicate that VIP and PACAP analogs act on molecular and cellular processes that could reduce aggressiveness of high-risk NB.
authors.affiliation: Université de Poitiers, Équipe Récepteurs, Régulations et Cellules Tumorales (2RCT), Pôle Biologie Santé, Bât. B36/B37, UFR Sciences Fondamentales et Appliquées, 1 rue Georges Bonnet TSA, 51106 86073 Poitiers Cedex 9, France.
authors.forename: Madryssa
authors.initials: M
authors.lastname: de Boisvilliers
authors.affiliation: Université de Poitiers, Équipe Récepteurs, Régulations et Cellules Tumorales (2RCT), Pôle Biologie Santé, Bât. B36/B37, UFR Sciences Fondamentales et Appliquées, 1 rue Georges Bonnet TSA, 51106 86073 Poitiers Cedex 9, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Perrin
authors.affiliation: Université de Poitiers, Équipe Récepteurs, Régulations et Cellules Tumorales (2RCT), Pôle Biologie Santé, Bât. B36/B37, UFR Sciences Fondamentales et Appliquées, 1 rue Georges Bonnet TSA, 51106 86073 Poitiers Cedex 9, France.
authors.forename: Salima
authors.initials: S
authors.lastname: Hebache
authors.affiliation: Université de Poitiers, Équipe Récepteurs, Régulations et Cellules Tumorales (2RCT), Pôle Biologie Santé, Bât. B36/B37, UFR Sciences Fondamentales et Appliquées, 1 rue Georges Bonnet TSA, 51106 86073 Poitiers Cedex 9, France.
authors.forename: Annie-Claire
authors.initials: AC
authors.lastname: Balandre
authors.affiliation: Université de Poitiers, Équipe Récepteurs, Régulations et Cellules Tumorales (2RCT), Pôle Biologie Santé, Bât. B36/B37, UFR Sciences Fondamentales et Appliquées, 1 rue Georges Bonnet TSA, 51106 86073 Poitiers Cedex 9, France.
authors.forename: Souheyla
authors.initials: S
authors.lastname: Bensalma
authors.affiliation: Université de Poitiers, Équipe Récepteurs, Régulations et Cellules Tumorales (2RCT), Pôle Biologie Santé, Bât. B36/B37, UFR Sciences Fondamentales et Appliquées, 1 rue Georges Bonnet TSA, 51106 86073 Poitiers Cedex 9, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Garnier
authors.affiliation: Université de Rouen, INSERM U982, Equipe Neuropeptides, survie neuronale et plasticité cellulaire, IRIB, UFR Sciences et Techniques, Place E. Blondel, 76821 Mont-Saint-Aignan, France.
authors.forename: David
authors.initials: D
authors.lastname: Vaudry
authors.affiliation: INRS, Institut Armand-Frappier, 531 boul. des Prairies, Laval, QC H7V 1B7, Canada.
authors.forename: Alain
authors.initials: A
authors.lastname: Fournier
authors.affiliation: Université de la Réunion, Stemcis c/o CYROI, 2, rue Maxime Rivière, 97490 Sainte Clotilde, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Festy
authors.affiliation: Université de Poitiers, Équipe Récepteurs, Régulations et Cellules Tumorales (2RCT), Pôle Biologie Santé, Bât. B36/B37, UFR Sciences Fondamentales et Appliquées, 1 rue Georges Bonnet TSA, 51106 86073 Poitiers Cedex 9, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Muller
authors.affiliation: Université de Poitiers, Équipe Récepteurs, Régulations et Cellules Tumorales (2RCT), Pôle Biologie Santé, Bât. B36/B37, UFR Sciences Fondamentales et Appliquées, 1 rue Georges Bonnet TSA, 51106 86073 Poitiers Cedex 9, France. Electronic address: corinne.chadeneau@univ-poitiers.fr.
authors.forename: Corinne
authors.initials: C
authors.lastname: Chadéneau
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009154:Mutation; D000071447:N-Myc Proto-Oncogene Protein / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000138:chemical synthesis / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000235:genetics / Q000378:metabolism; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000235:genetics / Q000378:metabolism; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014660:Vasoactive Intestinal Peptide / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: C495401:ADCYAP1 protein, human; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: AKT; ALK; Differentiation; Invasion; MYCN; PKA