Fibroblasts induce epithelial to mesenchymal transition in breast tumor cells which is prevented by fibroblasts treatment with histamine in high concentration

Autores
Porretti, Juliana Carla; Mohamad, Nora A.; Martin, Gabriela Adriana; Cricco, Graciela P.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Epithelial to mesenchymal transition (EMT) of cancer cells is an essential process in cancer progression. Cancer cells that undergone EMT loose cell–cell contacts, acquire mesenchymal properties and develop migratory and invasive abilities. In previous studies we have demonstrated that histamine may modify the invasive phenotype of pancreatic and mammary tumor cells. In this work we proposed to investigate whether histamine may also influence the interaction between tumor cells and normal fibroblasts. The potential activation of normal CCD-1059Sk fibroblasts by histamine and EMT phenotypic changes induced in MCF-7 and MDA-MB-231 breast tumor cells by the conditioned media (CM) derived from fibroblasts were evaluated. Initially, we determined the presence of H1, H2 and H4 histamine receptors and matrix metalloproteinase 2 (MMP2) mRNA in CCD-1059Sk fibroblasts. MMP2 gelatinolytic activity, cell migration and alpha-smooth muscle actin expression were increased in fibroblasts by low doses (<1 μM) and decreased by high doses (20 μM) of histamine. MCF-7 cells cultured with CM from fibroblasts exhibited spindle-shaped morphology, cell spreading and cytoplasmic expression of β-catenin but there was no change in MMP2 activity and cell migration. MDA-MB-231 cells cultured with CM from fibroblasts showed a more elongated phenotype, cell spreading, cytoplasmic β-catenin, increased MMP2 activity and endogenous TGF-β1 expression, and enhanced cell migration and invasion. Notably, all these features were reversed when mammary tumor cells were cultured with CM from fibroblasts treated with 20 μM histamine. In conclusion, high doses of histamine may prevent the activation of fibroblasts and also avert the EMT related changes induced in epithelial tumor cells by fibroblasts CM.
Fil: Porretti, Juliana Carla. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mohamad, Nora A.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Martin, Gabriela Adriana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cricco, Graciela P.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Materia
Breast Cancer
Fibroblasts
Histamine
Cell Migration
Epithelial to Mesenchymal Transition
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/16783
Acceder
id CONICETDig_2f0ee2d4dfb6869136d74ede6897226f
oai_identifier_str oai:ri.conicet.gov.ar:11336/16783
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Fibroblasts induce epithelial to mesenchymal transition in breast tumor cells which is prevented by fibroblasts treatment with histamine in high concentrationPorretti, Juliana CarlaMohamad, Nora A.Martin, Gabriela AdrianaCricco, Graciela P.Breast CancerFibroblastsHistamineCell MigrationEpithelial to Mesenchymal Transitionhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Epithelial to mesenchymal transition (EMT) of cancer cells is an essential process in cancer progression. Cancer cells that undergone EMT loose cell–cell contacts, acquire mesenchymal properties and develop migratory and invasive abilities. In previous studies we have demonstrated that histamine may modify the invasive phenotype of pancreatic and mammary tumor cells. In this work we proposed to investigate whether histamine may also influence the interaction between tumor cells and normal fibroblasts. The potential activation of normal CCD-1059Sk fibroblasts by histamine and EMT phenotypic changes induced in MCF-7 and MDA-MB-231 breast tumor cells by the conditioned media (CM) derived from fibroblasts were evaluated. Initially, we determined the presence of H1, H2 and H4 histamine receptors and matrix metalloproteinase 2 (MMP2) mRNA in CCD-1059Sk fibroblasts. MMP2 gelatinolytic activity, cell migration and alpha-smooth muscle actin expression were increased in fibroblasts by low doses (<1 μM) and decreased by high doses (20 μM) of histamine. MCF-7 cells cultured with CM from fibroblasts exhibited spindle-shaped morphology, cell spreading and cytoplasmic expression of β-catenin but there was no change in MMP2 activity and cell migration. MDA-MB-231 cells cultured with CM from fibroblasts showed a more elongated phenotype, cell spreading, cytoplasmic β-catenin, increased MMP2 activity and endogenous TGF-β1 expression, and enhanced cell migration and invasion. Notably, all these features were reversed when mammary tumor cells were cultured with CM from fibroblasts treated with 20 μM histamine. In conclusion, high doses of histamine may prevent the activation of fibroblasts and also avert the EMT related changes induced in epithelial tumor cells by fibroblasts CM.Fil: Porretti, Juliana Carla. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mohamad, Nora A.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Martin, Gabriela Adriana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cricco, Graciela P.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaElsevier2014-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/16783Porretti, Juliana Carla; Mohamad, Nora A.; Martin, Gabriela Adriana; Cricco, Graciela P.; Fibroblasts induce epithelial to mesenchymal transition in breast tumor cells which is prevented by fibroblasts treatment with histamine in high concentration; Elsevier; International Journal Of Biochemistry And Cellular Biology; 51; 6-2014; 29-381357-2725enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1357272514000910info:eu-repo/semantics/altIdentifier/doi/10.1016/j.biocel.2014.03.016info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:59Zoai:ri.conicet.gov.ar:11336/16783instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:57:59.908CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Fibroblasts induce epithelial to mesenchymal transition in breast tumor cells which is prevented by fibroblasts treatment with histamine in high concentration
title Fibroblasts induce epithelial to mesenchymal transition in breast tumor cells which is prevented by fibroblasts treatment with histamine in high concentration
spellingShingle Fibroblasts induce epithelial to mesenchymal transition in breast tumor cells which is prevented by fibroblasts treatment with histamine in high concentration
Porretti, Juliana Carla
Breast Cancer
Fibroblasts
Histamine
Cell Migration
Epithelial to Mesenchymal Transition
title_short Fibroblasts induce epithelial to mesenchymal transition in breast tumor cells which is prevented by fibroblasts treatment with histamine in high concentration
title_full Fibroblasts induce epithelial to mesenchymal transition in breast tumor cells which is prevented by fibroblasts treatment with histamine in high concentration
title_fullStr Fibroblasts induce epithelial to mesenchymal transition in breast tumor cells which is prevented by fibroblasts treatment with histamine in high concentration
title_full_unstemmed Fibroblasts induce epithelial to mesenchymal transition in breast tumor cells which is prevented by fibroblasts treatment with histamine in high concentration
title_sort Fibroblasts induce epithelial to mesenchymal transition in breast tumor cells which is prevented by fibroblasts treatment with histamine in high concentration
dc.creator.none.fl_str_mv Porretti, Juliana Carla
Mohamad, Nora A.
Martin, Gabriela Adriana
Cricco, Graciela P.
author Porretti, Juliana Carla
author_facet Porretti, Juliana Carla
Mohamad, Nora A.
Martin, Gabriela Adriana
Cricco, Graciela P.
author_role author
author2 Mohamad, Nora A.
Martin, Gabriela Adriana
Cricco, Graciela P.
author2_role author
author
author
dc.subject.none.fl_str_mv Breast Cancer
Fibroblasts
Histamine
Cell Migration
Epithelial to Mesenchymal Transition
topic Breast Cancer
Fibroblasts
Histamine
Cell Migration
Epithelial to Mesenchymal Transition
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Epithelial to mesenchymal transition (EMT) of cancer cells is an essential process in cancer progression. Cancer cells that undergone EMT loose cell–cell contacts, acquire mesenchymal properties and develop migratory and invasive abilities. In previous studies we have demonstrated that histamine may modify the invasive phenotype of pancreatic and mammary tumor cells. In this work we proposed to investigate whether histamine may also influence the interaction between tumor cells and normal fibroblasts. The potential activation of normal CCD-1059Sk fibroblasts by histamine and EMT phenotypic changes induced in MCF-7 and MDA-MB-231 breast tumor cells by the conditioned media (CM) derived from fibroblasts were evaluated. Initially, we determined the presence of H1, H2 and H4 histamine receptors and matrix metalloproteinase 2 (MMP2) mRNA in CCD-1059Sk fibroblasts. MMP2 gelatinolytic activity, cell migration and alpha-smooth muscle actin expression were increased in fibroblasts by low doses (<1 μM) and decreased by high doses (20 μM) of histamine. MCF-7 cells cultured with CM from fibroblasts exhibited spindle-shaped morphology, cell spreading and cytoplasmic expression of β-catenin but there was no change in MMP2 activity and cell migration. MDA-MB-231 cells cultured with CM from fibroblasts showed a more elongated phenotype, cell spreading, cytoplasmic β-catenin, increased MMP2 activity and endogenous TGF-β1 expression, and enhanced cell migration and invasion. Notably, all these features were reversed when mammary tumor cells were cultured with CM from fibroblasts treated with 20 μM histamine. In conclusion, high doses of histamine may prevent the activation of fibroblasts and also avert the EMT related changes induced in epithelial tumor cells by fibroblasts CM.
Fil: Porretti, Juliana Carla. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mohamad, Nora A.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Martin, Gabriela Adriana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cricco, Graciela P.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
description Epithelial to mesenchymal transition (EMT) of cancer cells is an essential process in cancer progression. Cancer cells that undergone EMT loose cell–cell contacts, acquire mesenchymal properties and develop migratory and invasive abilities. In previous studies we have demonstrated that histamine may modify the invasive phenotype of pancreatic and mammary tumor cells. In this work we proposed to investigate whether histamine may also influence the interaction between tumor cells and normal fibroblasts. The potential activation of normal CCD-1059Sk fibroblasts by histamine and EMT phenotypic changes induced in MCF-7 and MDA-MB-231 breast tumor cells by the conditioned media (CM) derived from fibroblasts were evaluated. Initially, we determined the presence of H1, H2 and H4 histamine receptors and matrix metalloproteinase 2 (MMP2) mRNA in CCD-1059Sk fibroblasts. MMP2 gelatinolytic activity, cell migration and alpha-smooth muscle actin expression were increased in fibroblasts by low doses (<1 μM) and decreased by high doses (20 μM) of histamine. MCF-7 cells cultured with CM from fibroblasts exhibited spindle-shaped morphology, cell spreading and cytoplasmic expression of β-catenin but there was no change in MMP2 activity and cell migration. MDA-MB-231 cells cultured with CM from fibroblasts showed a more elongated phenotype, cell spreading, cytoplasmic β-catenin, increased MMP2 activity and endogenous TGF-β1 expression, and enhanced cell migration and invasion. Notably, all these features were reversed when mammary tumor cells were cultured with CM from fibroblasts treated with 20 μM histamine. In conclusion, high doses of histamine may prevent the activation of fibroblasts and also avert the EMT related changes induced in epithelial tumor cells by fibroblasts CM.
publishDate 2014
dc.date.none.fl_str_mv 2014-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/16783
Porretti, Juliana Carla; Mohamad, Nora A.; Martin, Gabriela Adriana; Cricco, Graciela P.; Fibroblasts induce epithelial to mesenchymal transition in breast tumor cells which is prevented by fibroblasts treatment with histamine in high concentration; Elsevier; International Journal Of Biochemistry And Cellular Biology; 51; 6-2014; 29-38
1357-2725
url http://hdl.handle.net/11336/16783
identifier_str_mv Porretti, Juliana Carla; Mohamad, Nora A.; Martin, Gabriela Adriana; Cricco, Graciela P.; Fibroblasts induce epithelial to mesenchymal transition in breast tumor cells which is prevented by fibroblasts treatment with histamine in high concentration; Elsevier; International Journal Of Biochemistry And Cellular Biology; 51; 6-2014; 29-38
1357-2725
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1357272514000910
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.biocel.2014.03.016
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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