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VIP and PACAP analogs regulate therapeutic targets in high-risk neuroblastoma cells

de Boisvilliers, Madryssa; Perrin, Florian; Hebache, Salima; Balandre, Annie-Claire; Bensalma, Souheyla; Garnier, Agnes; Vaudry, David; Fournier, Alain; Festy, Franck; Muller, Jean-Marc; Chadeneau, Corinne (2016). VIP and PACAP analogs regulate therapeutic targets in high-risk neuroblastoma cells Peptides , vol. 78 . p. 30-41. DOI: 10.1016/j.peptides.2016.01.014.

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Résumé

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Neuroblastoma (NB) is a pediatric cancer. High-risk NB are characterized by poor differentiation, amplification of MYCN and mutations of ALK. Therapies are developed 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. VIP levels increase with NB differentiation. Here, the effects of VIP and PACAP analogs developed for therapeutic use were studied in MYCN-amplified SK-N-DZ and IMR-32 cells and in Kelly cells that in addition present the F1174L ALK mutation. As we previously observed for IMR-32 cells, VIP induced neuritogenesis in SK-N-DZ and Kelly cells, and it reduced MYCN expression in Kelly cells but not in SK-N-DZ cells. In parallel to its effect on MYCN expression, VIP decreased invasion in IMR-32 and Kelly cells. It also reduced AKT activity in the ALKmutated Kelly cells. Among the five PACAP analogs tested, [Hyp2]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.

Type de document:
Informations complémentaires: Résumé avec symboles
Mots-clés libres: MYCN, ALK, AKT, PKA, invasion, differentiation
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 30 août 2016 13:52
Dernière modification: 30 janv. 2017 10:10
URI: http://espace.inrs.ca/id/eprint/4564

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