Complementary actions of melatonin on angiogenic factors,the angiopoietin/Tie2 axis and VEGF, in co-cultures of human endothelial and breast cancer cells

Melatonin exerts oncostatic activity in breast cancer through antiangiogenic actions. There, the aim of the present study was to ascertain whether melatonin modulates, in a coordinated action, angiopoietin-1 (ANG-1), ANG-2, their cognate Tie2 receptor and VEGF in co-cultures of human endothelial cel...

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Autores: González González, Alicia, González Cabeza, Alicia Verónica|||0000-0003-4365-1770, Alonso González, Carolina|||0000-0002-3049-1408, Menéndez Menéndez, Javier, Martínez Campa, Carlos Manuel, Cos Corral, Samuel|||0000-0003-4900-8516
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad de Cantabria (UC)
Repositorio:UCrea Repositorio Abierto de la Universidad de Cantabria
Idioma:inglés
OAI Identifier:oai:repositorio.unican.es:10902/15470
Acceso en línea:http://hdl.handle.net/10902/15470
Access Level:acceso abierto
Palabra clave:Melatonin
Endothelial Cells
Breast Cancer
Angiopoietins
HUVEC
VEGF
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spelling Complementary actions of melatonin on angiogenic factors,the angiopoietin/Tie2 axis and VEGF, in co-cultures of human endothelial and breast cancer cellsGonzález González, AliciaGonzález Cabeza, Alicia Verónica|||0000-0003-4365-1770Alonso González, Carolina|||0000-0002-3049-1408Menéndez Menéndez, JavierMartínez Campa, Carlos ManuelCos Corral, Samuel|||0000-0003-4900-8516MelatoninEndothelial CellsBreast CancerAngiopoietinsHUVECVEGFMelatonin exerts oncostatic activity in breast cancer through antiangiogenic actions. There, the aim of the present study was to ascertain whether melatonin modulates, in a coordinated action, angiopoietin-1 (ANG-1), ANG-2, their cognate Tie2 receptor and VEGF in co-cultures of human endothelial cells (HUVECs) and breast cancer (MCF-7) cells. To accomplish this we used co-cultures of human breast cancer cells (MCF-7) or non-malignant human mammary epithelial cells (MCF?10A) with endothelial cells (HUVECs). The presence of breast cancer cells increased HUVEC proliferation and 1 mM melatonin prevented this effect. ANG-1, ANG-2 and VEGF levels in co-culture media and mRNA expression were upregulated and Tie2 mRNA expression was downregulated in the HUVECs and MCF-7. Melatonin (1 mM) downregulated ANG-1, ANG-2 and VEGF levels in the co-culture media and mRNA expression in both types of cells and upregulated Tie2 mRNA expression in HUVECs. ANG-1, ANG-2, Tie2 and VEGF mRNA expression were not modified during HUVEC/MCF-10A co-culture. Estradiol (10 nM) increased ANG-1, ANG-2 and VEGF mRNA expression in HUVECs and melatonin (1 mM) counteracted this effect. We conclude that melatonin simultaneously coordinates downregulation of angiopoietins with a reduction in VEGF, which could be an effective therapeutic strategy for blocking tumor angiogenesis.The present study was supported by grants from the Spanish Economy and Competitiveness Ministry (SAF2013-42012-P, SAF2016-77103-P), and from the Instituto de Investigación Sanitaria Valdecilla (IDIVAL) (APG/12).Spandidos PublicationsUniversidad de Cantabria20182018-01-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttp://hdl.handle.net/10902/15470Oncol Rep. 2018 Jan;39(1):433-441reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/154702026-06-02T12:39:31Z
dc.title.none.fl_str_mv Complementary actions of melatonin on angiogenic factors,the angiopoietin/Tie2 axis and VEGF, in co-cultures of human endothelial and breast cancer cells
title Complementary actions of melatonin on angiogenic factors,the angiopoietin/Tie2 axis and VEGF, in co-cultures of human endothelial and breast cancer cells
spellingShingle Complementary actions of melatonin on angiogenic factors,the angiopoietin/Tie2 axis and VEGF, in co-cultures of human endothelial and breast cancer cells
González González, Alicia
Melatonin
Endothelial Cells
Breast Cancer
Angiopoietins
HUVEC
VEGF
title_short Complementary actions of melatonin on angiogenic factors,the angiopoietin/Tie2 axis and VEGF, in co-cultures of human endothelial and breast cancer cells
title_full Complementary actions of melatonin on angiogenic factors,the angiopoietin/Tie2 axis and VEGF, in co-cultures of human endothelial and breast cancer cells
title_fullStr Complementary actions of melatonin on angiogenic factors,the angiopoietin/Tie2 axis and VEGF, in co-cultures of human endothelial and breast cancer cells
title_full_unstemmed Complementary actions of melatonin on angiogenic factors,the angiopoietin/Tie2 axis and VEGF, in co-cultures of human endothelial and breast cancer cells
title_sort Complementary actions of melatonin on angiogenic factors,the angiopoietin/Tie2 axis and VEGF, in co-cultures of human endothelial and breast cancer cells
dc.creator.none.fl_str_mv González González, Alicia
González Cabeza, Alicia Verónica|||0000-0003-4365-1770
Alonso González, Carolina|||0000-0002-3049-1408
Menéndez Menéndez, Javier
Martínez Campa, Carlos Manuel
Cos Corral, Samuel|||0000-0003-4900-8516
author González González, Alicia
author_facet González González, Alicia
González Cabeza, Alicia Verónica|||0000-0003-4365-1770
Alonso González, Carolina|||0000-0002-3049-1408
Menéndez Menéndez, Javier
Martínez Campa, Carlos Manuel
Cos Corral, Samuel|||0000-0003-4900-8516
author_role author
author2 González Cabeza, Alicia Verónica|||0000-0003-4365-1770
Alonso González, Carolina|||0000-0002-3049-1408
Menéndez Menéndez, Javier
Martínez Campa, Carlos Manuel
Cos Corral, Samuel|||0000-0003-4900-8516
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad de Cantabria
dc.subject.none.fl_str_mv Melatonin
Endothelial Cells
Breast Cancer
Angiopoietins
HUVEC
VEGF
topic Melatonin
Endothelial Cells
Breast Cancer
Angiopoietins
HUVEC
VEGF
description Melatonin exerts oncostatic activity in breast cancer through antiangiogenic actions. There, the aim of the present study was to ascertain whether melatonin modulates, in a coordinated action, angiopoietin-1 (ANG-1), ANG-2, their cognate Tie2 receptor and VEGF in co-cultures of human endothelial cells (HUVECs) and breast cancer (MCF-7) cells. To accomplish this we used co-cultures of human breast cancer cells (MCF-7) or non-malignant human mammary epithelial cells (MCF?10A) with endothelial cells (HUVECs). The presence of breast cancer cells increased HUVEC proliferation and 1 mM melatonin prevented this effect. ANG-1, ANG-2 and VEGF levels in co-culture media and mRNA expression were upregulated and Tie2 mRNA expression was downregulated in the HUVECs and MCF-7. Melatonin (1 mM) downregulated ANG-1, ANG-2 and VEGF levels in the co-culture media and mRNA expression in both types of cells and upregulated Tie2 mRNA expression in HUVECs. ANG-1, ANG-2, Tie2 and VEGF mRNA expression were not modified during HUVEC/MCF-10A co-culture. Estradiol (10 nM) increased ANG-1, ANG-2 and VEGF mRNA expression in HUVECs and melatonin (1 mM) counteracted this effect. We conclude that melatonin simultaneously coordinates downregulation of angiopoietins with a reduction in VEGF, which could be an effective therapeutic strategy for blocking tumor angiogenesis.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-01-01
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/10902/15470
url http://hdl.handle.net/10902/15470
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
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
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Spandidos Publications
publisher.none.fl_str_mv Spandidos Publications
dc.source.none.fl_str_mv Oncol Rep. 2018 Jan;39(1):433-441
reponame:UCrea Repositorio Abierto de la Universidad de Cantabria
instname:Universidad de Cantabria (UC)
instname_str Universidad de Cantabria (UC)
reponame_str UCrea Repositorio Abierto de la Universidad de Cantabria
collection UCrea Repositorio Abierto de la Universidad de Cantabria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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