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

Madryssa de Boisvilliers (1) , Florian Perrin (1) , Salima Hebache (1) , Annie-Claire Balandre (1) , Souheyla Bensalma (1) , Agnès Garnier (1) , David Vaudry (2) , Alain Fournier (3) , Franck Festy (4) , Jean-Marc Muller (1) , Corinne Chadéneau (1)

1 UP - Université de Poitiers = University of Poitiers
2 UNIROUEN - Université de Rouen Normandie
3 INRS-IAF - Institut Armand Frappier
4 UR - Université de La Réunion

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.

Mots clés: AKT; ALK; Differentiation; Invasion; MYCN; PKA

Domaines: Sciences du Vivant [q-bio]

Madryssa de Boisvilliers, Florian Perrin, Salima Hebache, Annie-Claire Balandre, Souheyla Bensalma, et al.. VIP and PACAP analogs regulate therapeutic targets in high-risk neuroblastoma cells.. Peptides, 2016, 78, pp.30-41. ⟨10.1016/j.peptides.2016.01.014⟩. ⟨pasteur-01351076⟩