Stimulation of neuroendocrine differentiation in prostate cancer cells by GHRH and its blockade by GHRH antagonists.

Prostate cancer is the second leading cause of cancer-related deaths among men in developed countries. Neuroendocrine prostate cancer, in particular, is associated with an aggressive phenotype and a poor prognosis. Neuroendocrine cells produce and secrete peptide hormones and growth factors in a par...

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Autores: Muñoz Moreno, Laura|||0000-0002-2322-8986, Carmena Sierra, María José|||0000-0002-5602-0014, Schally, Andrew Victor, Prieto Villapún, Juan Carlos, Bajo Chueca, Ana María|||0000-0002-4944-4222
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad de Alcalá (UAH)
Repositorio:e_Buah Biblioteca Digital Universidad de Alcalá
Idioma:inglés
OAI Identifier:oai:ebuah.uah.es:10017/59345
Acceso en línea:http://hdl.handle.net/10017/59345
https://dx.doi.org/10.1007/s10637-019-00831-2
Access Level:acceso abierto
Palabra clave:GHRH
LNCaP cells
PC3 cells
Neuroendocrine differentiation
Exosomes
Prostate cancer
Medicina
Medicine
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network_acronym_str ES
network_name_str España
repository_id_str
spelling Stimulation of neuroendocrine differentiation in prostate cancer cells by GHRH and its blockade by GHRH antagonists.Muñoz Moreno, Laura|||0000-0002-2322-8986Carmena Sierra, María José|||0000-0002-5602-0014Schally, Andrew VictorPrieto Villapún, Juan CarlosBajo Chueca, Ana María|||0000-0002-4944-4222GHRHLNCaP cellsPC3 cellsNeuroendocrine differentiationExosomesProstate cancerMedicinaMedicineProstate cancer is the second leading cause of cancer-related deaths among men in developed countries. Neuroendocrine prostate cancer, in particular, is associated with an aggressive phenotype and a poor prognosis. Neuroendocrine cells produce and secrete peptide hormones and growth factors in a paracrine/autocrine manner which promote the progression of the disease. Recent studies have demonstrated that extracellular vesicles or exosomes are released by prostate cancer cells, supporting the spread of prostate cancer. Hence, the aim of this study was to investigate the effect of growth hormone-releasing hormone (GHRH) on neuroendocrine differentiation (NED) in the androgen-dependent prostate cancer cell line LNCaP and the molecular mechanisms underlying these effects. GHRH induced an increase in the percentage of neurite-bearing cells and in the protein levels of Neuron-Specific Enolase. Both effects were blocked by the GHRH receptor antagonist MIA-690. In addition, pretreatment of these cells with the calcium chelator BAPTA, the EGFR inhibitor AG-1478 or the HER2 inhibitor AG-825 reduced the effect of GHRH, suggesting that the GHRH-induced stimulation of NED involves calcium channel activation and EGFR/HER2 transactivation. Finally, PC3-derived exosomes led to an increase in NED, cell proliferation and cell adhesion. Altogether, these findings suggest that GHRH antagonists should be considered for in the management of neuroendocrine prostate cancer.Universidad de Alcalá20202020-07-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10017/59345https://dx.doi.org/10.1007/s10637-019-00831-2reponame:e_Buah Biblioteca Digital Universidad de Alcaláinstname:Universidad de Alcalá (UAH)InglésengUAH Not available CCG2015%2FBIO-010UAH Not available CCG2014%2FBIO-028open accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ebuah.uah.es:10017/593452026-06-18T11:13:07Z
dc.title.none.fl_str_mv Stimulation of neuroendocrine differentiation in prostate cancer cells by GHRH and its blockade by GHRH antagonists.
title Stimulation of neuroendocrine differentiation in prostate cancer cells by GHRH and its blockade by GHRH antagonists.
spellingShingle Stimulation of neuroendocrine differentiation in prostate cancer cells by GHRH and its blockade by GHRH antagonists.
Muñoz Moreno, Laura|||0000-0002-2322-8986
GHRH
LNCaP cells
PC3 cells
Neuroendocrine differentiation
Exosomes
Prostate cancer
Medicina
Medicine
title_short Stimulation of neuroendocrine differentiation in prostate cancer cells by GHRH and its blockade by GHRH antagonists.
title_full Stimulation of neuroendocrine differentiation in prostate cancer cells by GHRH and its blockade by GHRH antagonists.
title_fullStr Stimulation of neuroendocrine differentiation in prostate cancer cells by GHRH and its blockade by GHRH antagonists.
title_full_unstemmed Stimulation of neuroendocrine differentiation in prostate cancer cells by GHRH and its blockade by GHRH antagonists.
title_sort Stimulation of neuroendocrine differentiation in prostate cancer cells by GHRH and its blockade by GHRH antagonists.
dc.creator.none.fl_str_mv Muñoz Moreno, Laura|||0000-0002-2322-8986
Carmena Sierra, María José|||0000-0002-5602-0014
Schally, Andrew Victor
Prieto Villapún, Juan Carlos
Bajo Chueca, Ana María|||0000-0002-4944-4222
author Muñoz Moreno, Laura|||0000-0002-2322-8986
author_facet Muñoz Moreno, Laura|||0000-0002-2322-8986
Carmena Sierra, María José|||0000-0002-5602-0014
Schally, Andrew Victor
Prieto Villapún, Juan Carlos
Bajo Chueca, Ana María|||0000-0002-4944-4222
author_role author
author2 Carmena Sierra, María José|||0000-0002-5602-0014
Schally, Andrew Victor
Prieto Villapún, Juan Carlos
Bajo Chueca, Ana María|||0000-0002-4944-4222
author2_role author
author
author
author
dc.subject.none.fl_str_mv GHRH
LNCaP cells
PC3 cells
Neuroendocrine differentiation
Exosomes
Prostate cancer
Medicina
Medicine
topic GHRH
LNCaP cells
PC3 cells
Neuroendocrine differentiation
Exosomes
Prostate cancer
Medicina
Medicine
description Prostate cancer is the second leading cause of cancer-related deaths among men in developed countries. Neuroendocrine prostate cancer, in particular, is associated with an aggressive phenotype and a poor prognosis. Neuroendocrine cells produce and secrete peptide hormones and growth factors in a paracrine/autocrine manner which promote the progression of the disease. Recent studies have demonstrated that extracellular vesicles or exosomes are released by prostate cancer cells, supporting the spread of prostate cancer. Hence, the aim of this study was to investigate the effect of growth hormone-releasing hormone (GHRH) on neuroendocrine differentiation (NED) in the androgen-dependent prostate cancer cell line LNCaP and the molecular mechanisms underlying these effects. GHRH induced an increase in the percentage of neurite-bearing cells and in the protein levels of Neuron-Specific Enolase. Both effects were blocked by the GHRH receptor antagonist MIA-690. In addition, pretreatment of these cells with the calcium chelator BAPTA, the EGFR inhibitor AG-1478 or the HER2 inhibitor AG-825 reduced the effect of GHRH, suggesting that the GHRH-induced stimulation of NED involves calcium channel activation and EGFR/HER2 transactivation. Finally, PC3-derived exosomes led to an increase in NED, cell proliferation and cell adhesion. Altogether, these findings suggest that GHRH antagonists should be considered for in the management of neuroendocrine prostate cancer.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-07-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10017/59345
https://dx.doi.org/10.1007/s10637-019-00831-2
url http://hdl.handle.net/10017/59345
https://dx.doi.org/10.1007/s10637-019-00831-2
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv UAH Not available CCG2015%2FBIO-010
UAH Not available CCG2014%2FBIO-028
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:e_Buah Biblioteca Digital Universidad de Alcalá
instname:Universidad de Alcalá (UAH)
instname_str Universidad de Alcalá (UAH)
reponame_str e_Buah Biblioteca Digital Universidad de Alcalá
collection e_Buah Biblioteca Digital Universidad de Alcalá
repository.name.fl_str_mv
repository.mail.fl_str_mv
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