PACAP and VIP Inhibit the Invasiveness of Glioblastoma Cells Exposed to Hypoxia through the Regulation of HIFs and EGFR Expression

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) through the binding of vasoactive intestinal peptide receptors (VIPRs), perform a wide variety of effects in human cancers, including glioblastoma multiforme (GBM). This tumor is characterized by exten...

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Autores principales: Maugeri, Grazia, D’Amico, Agata Grazia, Reitano, Rita, Magro, Gaetano, Cavallaro, Sebastiano, Salomone, Salvatore, D’Agata, Velia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885839/
https://www.ncbi.nlm.nih.gov/pubmed/27303300
http://dx.doi.org/10.3389/fphar.2016.00139
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author Maugeri, Grazia
D’Amico, Agata Grazia
Reitano, Rita
Magro, Gaetano
Cavallaro, Sebastiano
Salomone, Salvatore
D’Agata, Velia
author_facet Maugeri, Grazia
D’Amico, Agata Grazia
Reitano, Rita
Magro, Gaetano
Cavallaro, Sebastiano
Salomone, Salvatore
D’Agata, Velia
author_sort Maugeri, Grazia
collection PubMed
description Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) through the binding of vasoactive intestinal peptide receptors (VIPRs), perform a wide variety of effects in human cancers, including glioblastoma multiforme (GBM). This tumor is characterized by extensive areas of hypoxia, which triggers the expression of hypoxia-inducible factors (HIFs). HIFs not only mediate angiogenesis but also tumor cell migration and invasion. Furthermore, HIFs activation is linked to epidermal growth factor receptor (EGFR) overexpression. Previous studies have shown that VIP interferes with the invasive nature of gliomas by regulating cell migration. However, the role of VIP family members in GBM infiltration under low oxygen tension has not been clarified yet. Therefore, in the present study we have investigated, for the first time, the molecular mechanisms involved in the anti-invasive effect of PACAP or VIP in U87MG glioblastoma cells exposed to hypoxia induced by treatment with desferrioxamine (DFX). The results suggest that either PACAP or VIP exert an anti-infiltrative effect under low oxygen tension by modulating HIFs and EGFR expression, key elements involved in cell migration and angiogenesis. These peptides act through the inhibition of PI3K/Akt and MAPK/ERK signaling pathways, which are known to have a crucial role in HIFs regulation.
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spelling pubmed-48858392016-06-14 PACAP and VIP Inhibit the Invasiveness of Glioblastoma Cells Exposed to Hypoxia through the Regulation of HIFs and EGFR Expression Maugeri, Grazia D’Amico, Agata Grazia Reitano, Rita Magro, Gaetano Cavallaro, Sebastiano Salomone, Salvatore D’Agata, Velia Front Pharmacol Pharmacology Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) through the binding of vasoactive intestinal peptide receptors (VIPRs), perform a wide variety of effects in human cancers, including glioblastoma multiforme (GBM). This tumor is characterized by extensive areas of hypoxia, which triggers the expression of hypoxia-inducible factors (HIFs). HIFs not only mediate angiogenesis but also tumor cell migration and invasion. Furthermore, HIFs activation is linked to epidermal growth factor receptor (EGFR) overexpression. Previous studies have shown that VIP interferes with the invasive nature of gliomas by regulating cell migration. However, the role of VIP family members in GBM infiltration under low oxygen tension has not been clarified yet. Therefore, in the present study we have investigated, for the first time, the molecular mechanisms involved in the anti-invasive effect of PACAP or VIP in U87MG glioblastoma cells exposed to hypoxia induced by treatment with desferrioxamine (DFX). The results suggest that either PACAP or VIP exert an anti-infiltrative effect under low oxygen tension by modulating HIFs and EGFR expression, key elements involved in cell migration and angiogenesis. These peptides act through the inhibition of PI3K/Akt and MAPK/ERK signaling pathways, which are known to have a crucial role in HIFs regulation. Frontiers Media S.A. 2016-05-31 /pmc/articles/PMC4885839/ /pubmed/27303300 http://dx.doi.org/10.3389/fphar.2016.00139 Text en Copyright © 2016 Maugeri, D’Amico, Reitano, Magro, Cavallaro, Salomone and D’Agata. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Maugeri, Grazia
D’Amico, Agata Grazia
Reitano, Rita
Magro, Gaetano
Cavallaro, Sebastiano
Salomone, Salvatore
D’Agata, Velia
PACAP and VIP Inhibit the Invasiveness of Glioblastoma Cells Exposed to Hypoxia through the Regulation of HIFs and EGFR Expression
title PACAP and VIP Inhibit the Invasiveness of Glioblastoma Cells Exposed to Hypoxia through the Regulation of HIFs and EGFR Expression
title_full PACAP and VIP Inhibit the Invasiveness of Glioblastoma Cells Exposed to Hypoxia through the Regulation of HIFs and EGFR Expression
title_fullStr PACAP and VIP Inhibit the Invasiveness of Glioblastoma Cells Exposed to Hypoxia through the Regulation of HIFs and EGFR Expression
title_full_unstemmed PACAP and VIP Inhibit the Invasiveness of Glioblastoma Cells Exposed to Hypoxia through the Regulation of HIFs and EGFR Expression
title_short PACAP and VIP Inhibit the Invasiveness of Glioblastoma Cells Exposed to Hypoxia through the Regulation of HIFs and EGFR Expression
title_sort pacap and vip inhibit the invasiveness of glioblastoma cells exposed to hypoxia through the regulation of hifs and egfr expression
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885839/
https://www.ncbi.nlm.nih.gov/pubmed/27303300
http://dx.doi.org/10.3389/fphar.2016.00139
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