Neuropeptide gastrin-releasing peptide induces PI3K/reactive oxygen species–dependent migration in lung adenocarcinoma cells

Nerve fibers and neurotransmitters have increasingly been shown to have a role in tumor progression. Gastrin-releasing peptide is a neuropeptide linked to tumor aggressiveness, acting as an autocrine tumor growth factor by binding to its receptor, gastrin-releasing peptide receptor, expressed by man...

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Main Authors: Natália Jaeger, Rafael Sanguinetti Czepielewski, Maira Bagatini, Bárbara N Porto, Cristina Bonorino
Format: Article
Language:English
Published: SAGE Publishing 2017-03-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428317694321
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author Natália Jaeger
Rafael Sanguinetti Czepielewski
Maira Bagatini
Bárbara N Porto
Cristina Bonorino
author_facet Natália Jaeger
Rafael Sanguinetti Czepielewski
Maira Bagatini
Bárbara N Porto
Cristina Bonorino
author_sort Natália Jaeger
collection DOAJ
description Nerve fibers and neurotransmitters have increasingly been shown to have a role in tumor progression. Gastrin-releasing peptide is a neuropeptide linked to tumor aggressiveness, acting as an autocrine tumor growth factor by binding to its receptor, gastrin-releasing peptide receptor, expressed by many tumors. Although neuropeptides have been previously linked to tumor cell proliferation, more recent studies have uncovered roles for neuropeptides in chemotaxis and metastasis. Understanding the precise roles of such peptides in cancer is crucial to optimizing targeted therapy design. We have previously described that gastrin-releasing peptide acts directly as a chemotactic factor for neutrophils, dependent on PI3K, ERK, and p38. In this study, we investigated roles for gastrin-releasing peptide in lung adenocarcinoma. We asked if gastrin-releasing peptide would act as a proliferative and/or chemotactic stimulus for gastrin-releasing peptide receptor–expressing tumor cells. In A549 cells, a non-small cell lung carcinoma line, the treatment with gastrin-releasing peptide leads to activation of AKT and ERK1/2, and production of reactive oxygen species. Gastrin-releasing peptide induced migration of A549 cells, dependent on gastrin-releasing peptide receptor and PI3K, but not ERK. However, no proliferation was observed in these cells in response to gastrin-releasing peptide, and gastrin-releasing peptide did not promote resistance to treatment with a chemotherapy drug. Our results suggest that, similar to what happens in neutrophils, gastrin-releasing peptide is a migratory, rather than a proliferative, stimulus, for non–small cell lung carcinoma cells, indicating a putative role for gastrin-releasing peptide and gastrin-releasing peptide receptor in metastasis.
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spelling doaj-art-e60c1f29bab04bfbbbbc942c33c527d52025-08-20T03:38:44ZengSAGE PublishingTumor Biology1423-03802017-03-013910.1177/1010428317694321Neuropeptide gastrin-releasing peptide induces PI3K/reactive oxygen species–dependent migration in lung adenocarcinoma cellsNatália Jaeger0Rafael Sanguinetti Czepielewski1Maira Bagatini2Bárbara N Porto3Cristina Bonorino4Programa de Pós-Graduação em Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, BrazilPrograma de Pós-Graduação em Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, BrazilLaboratório de Imunologia Celular e Molecular, Hospital São Lucas, Instituto de Pesquisas Biomédicas (IPB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, BrazilLaboratório de Imunologia Clínica e Experimental, Hospital São Lucas, Instituto de Pesquisas Biomédicas (IPB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, BrazilPrograma de Pós-Graduação em Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, BrazilNerve fibers and neurotransmitters have increasingly been shown to have a role in tumor progression. Gastrin-releasing peptide is a neuropeptide linked to tumor aggressiveness, acting as an autocrine tumor growth factor by binding to its receptor, gastrin-releasing peptide receptor, expressed by many tumors. Although neuropeptides have been previously linked to tumor cell proliferation, more recent studies have uncovered roles for neuropeptides in chemotaxis and metastasis. Understanding the precise roles of such peptides in cancer is crucial to optimizing targeted therapy design. We have previously described that gastrin-releasing peptide acts directly as a chemotactic factor for neutrophils, dependent on PI3K, ERK, and p38. In this study, we investigated roles for gastrin-releasing peptide in lung adenocarcinoma. We asked if gastrin-releasing peptide would act as a proliferative and/or chemotactic stimulus for gastrin-releasing peptide receptor–expressing tumor cells. In A549 cells, a non-small cell lung carcinoma line, the treatment with gastrin-releasing peptide leads to activation of AKT and ERK1/2, and production of reactive oxygen species. Gastrin-releasing peptide induced migration of A549 cells, dependent on gastrin-releasing peptide receptor and PI3K, but not ERK. However, no proliferation was observed in these cells in response to gastrin-releasing peptide, and gastrin-releasing peptide did not promote resistance to treatment with a chemotherapy drug. Our results suggest that, similar to what happens in neutrophils, gastrin-releasing peptide is a migratory, rather than a proliferative, stimulus, for non–small cell lung carcinoma cells, indicating a putative role for gastrin-releasing peptide and gastrin-releasing peptide receptor in metastasis.https://doi.org/10.1177/1010428317694321
spellingShingle Natália Jaeger
Rafael Sanguinetti Czepielewski
Maira Bagatini
Bárbara N Porto
Cristina Bonorino
Neuropeptide gastrin-releasing peptide induces PI3K/reactive oxygen species–dependent migration in lung adenocarcinoma cells
Tumor Biology
title Neuropeptide gastrin-releasing peptide induces PI3K/reactive oxygen species–dependent migration in lung adenocarcinoma cells
title_full Neuropeptide gastrin-releasing peptide induces PI3K/reactive oxygen species–dependent migration in lung adenocarcinoma cells
title_fullStr Neuropeptide gastrin-releasing peptide induces PI3K/reactive oxygen species–dependent migration in lung adenocarcinoma cells
title_full_unstemmed Neuropeptide gastrin-releasing peptide induces PI3K/reactive oxygen species–dependent migration in lung adenocarcinoma cells
title_short Neuropeptide gastrin-releasing peptide induces PI3K/reactive oxygen species–dependent migration in lung adenocarcinoma cells
title_sort neuropeptide gastrin releasing peptide induces pi3k reactive oxygen species dependent migration in lung adenocarcinoma cells
url https://doi.org/10.1177/1010428317694321
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