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

Madryssa de Boisvilliers1, Florian Perrin1, Salima Hebache1

  • 1Université 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.

Peptides
|January 31, 2016
PubMed

Insights

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) analogs show potential in treating high-risk neuroblastoma (NB). These neuropeptides may reduce cancer aggressiveness by inhibiting MYCN and ALK signaling and decreasing cell invasion.

Area of Science:

  • Oncology
  • Neuroscience
  • Molecular Biology

Background:

  • Neuroblastoma (NB) is a pediatric cancer with high-risk subtypes requiring novel therapies.
  • Current treatments for high-risk NB focus on inducing cell differentiation and inhibiting MYCN and ALK signaling pathways.
  • Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are neuropeptides linked to NB differentiation.

Purpose of the Study:

  • To investigate the therapeutic potential of VIP and PACAP analogs in high-risk neuroblastoma.
  • To examine the effects of these neuropeptides on MYCN expression, ALK signaling, and cell invasion in NB cell lines.

Main Methods:

  • Studied VIP and PACAP analogs in MYCN-amplified NB cell lines (SK-N-DZ, IMR-32) and ALK-mutated Kelly cells.
  • Assessed effects on neuritogenesis, MYCN expression, AKT activity, and cell invasion.
  • Analyzed expression of VIP/PACAP receptors (VPAC1, VPAC2, PAC1).

Main Results:

  • VIP induced neuritogenesis and reduced MYCN expression and invasion in specific NB cell lines.
  • VIP decreased AKT activity in ALK-mutated cells, with PKA-dependent effects.
  • [Hyp(2)]PACAP-27 demonstrated higher efficacy than VIP in Kelly cells.
  • All tested NB cell lines expressed VPAC1, VPAC2, and PAC1 receptor genes.

Conclusions:

  • VIP and PACAP analogs exhibit potential for reducing the aggressiveness of high-risk neuroblastoma.
  • These neuropeptides modulate key molecular targets and cellular processes relevant to NB therapy.
  • Further research into VIP and PACAP analogs could lead to new therapeutic strategies for pediatric cancer.

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