VIP and PACAP analogs regulate therapeutic targets in high-risk neuroblastoma cells. - RIIP - Réseau International des Instituts Pasteur Access content directly
Journal Articles Peptides Year : 2016

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.

Dates and versions

pasteur-01351076 , version 1 (02-08-2016)

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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⟩
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