Hypoxia-induced nitric oxide release by luminal cells stimulates proliferation and uPA secretion of myoepithelial cells in a bicellular murine mammary tumor

Autores
Krasnapolski, Martin Alejandro; Lodillinsky, Catalina; Bal, Elisa Dora; Eijan, Ana Maria
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Introduction: LM38 murine mammary adenocarcinoma model is formed by LM38-LP (myoepithelial and luminal), LM38-HP (luminal) and LM38-D2 (myoepithelial) cell lines. In a previous work, we had shown that LM38-HP and LM38-D2 cell lines are less malignant than the bicellular LM38-LP cell line. Purpose: To study the role of nitric oxide (NO) as one of the mediators of functional interactions between malignant luminal and myoepithelial cells. Methods and results: Using immunohistochemistry, in vivo iNOS expression was only detected in the luminal cells of bicellular LM38-LP and most cells of LM38-HP tumors. In cobalt-induced pseudohypoxia, LM38-LP and LM38-HP cell lines significantly increased HIF-1α and iNOS expression (Western blotting) and therefore NO production (Griess method). This increase was inhibited by the iNOS inhibitor 1400 W. On the other side, NO was not detectable in LM38-D2 cells either in basal or in pseudohypoxia. In addition, pseudohypoxia increased urokinase-type plasminogen activator (uPA) secretion by LM38-LP and LM38-HP cells and migration in the LM38-LP cell line, without modulating these properties in LM38-D2 cells (radial caseinolysis). The NO donor DETA/NONOate (500 μM) was able to increase uPA secretion and in vitro growth of LM38-D2. In agreement, 1400 W prevented in vivo growth of the myoepithelial LM38-D2 cells. Conclusions: Hypoxia leads to an enhanced NO production by the luminal component, through HIF-1α and iNOS, which can stimulate myoepithelial cell proliferation and uPA secretion. In these new conditions, myoepithelial cells might act as an invasive forefront generating gaps that could help luminal cells to escape from the primary tumor.
Fil: Krasnapolski, Martin Alejandro. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lodillinsky, Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina. Institut Curie Research Center; Francia
Fil: Bal, Elisa Dora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
Fil: Eijan, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
Materia
Breast Cancer
Myoepithelial Cells
Hypoxia
Nitric Oxide
Luminal Cells
Migration
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/38864
Acceder
id CONICETDig_2eae37d696fcb4d4ceef4bf78cd5ab29
oai_identifier_str oai:ri.conicet.gov.ar:11336/38864
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Hypoxia-induced nitric oxide release by luminal cells stimulates proliferation and uPA secretion of myoepithelial cells in a bicellular murine mammary tumorKrasnapolski, Martin AlejandroLodillinsky, CatalinaBal, Elisa DoraEijan, Ana MariaBreast CancerMyoepithelial CellsHypoxiaNitric OxideLuminal CellsMigrationhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Introduction: LM38 murine mammary adenocarcinoma model is formed by LM38-LP (myoepithelial and luminal), LM38-HP (luminal) and LM38-D2 (myoepithelial) cell lines. In a previous work, we had shown that LM38-HP and LM38-D2 cell lines are less malignant than the bicellular LM38-LP cell line. Purpose: To study the role of nitric oxide (NO) as one of the mediators of functional interactions between malignant luminal and myoepithelial cells. Methods and results: Using immunohistochemistry, in vivo iNOS expression was only detected in the luminal cells of bicellular LM38-LP and most cells of LM38-HP tumors. In cobalt-induced pseudohypoxia, LM38-LP and LM38-HP cell lines significantly increased HIF-1α and iNOS expression (Western blotting) and therefore NO production (Griess method). This increase was inhibited by the iNOS inhibitor 1400 W. On the other side, NO was not detectable in LM38-D2 cells either in basal or in pseudohypoxia. In addition, pseudohypoxia increased urokinase-type plasminogen activator (uPA) secretion by LM38-LP and LM38-HP cells and migration in the LM38-LP cell line, without modulating these properties in LM38-D2 cells (radial caseinolysis). The NO donor DETA/NONOate (500 μM) was able to increase uPA secretion and in vitro growth of LM38-D2. In agreement, 1400 W prevented in vivo growth of the myoepithelial LM38-D2 cells. Conclusions: Hypoxia leads to an enhanced NO production by the luminal component, through HIF-1α and iNOS, which can stimulate myoepithelial cell proliferation and uPA secretion. In these new conditions, myoepithelial cells might act as an invasive forefront generating gaps that could help luminal cells to escape from the primary tumor.Fil: Krasnapolski, Martin Alejandro. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lodillinsky, Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina. Institut Curie Research Center; FranciaFil: Bal, Elisa Dora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; ArgentinaFil: Eijan, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; ArgentinaSpringer Heidelberg2015-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/38864Krasnapolski, Martin Alejandro; Lodillinsky, Catalina; Bal, Elisa Dora; Eijan, Ana Maria; Hypoxia-induced nitric oxide release by luminal cells stimulates proliferation and uPA secretion of myoepithelial cells in a bicellular murine mammary tumor; Springer Heidelberg; Journal Of Cancer Research And Clinical Oncology; 141; 10; 10-2015; 1727-17380171-52161432-1335CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s00432-015-1934-1info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00432-015-1934-1info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:30:58Zoai:ri.conicet.gov.ar:11336/38864instacron: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:34982025-09-29 10:30:58.773CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hypoxia-induced nitric oxide release by luminal cells stimulates proliferation and uPA secretion of myoepithelial cells in a bicellular murine mammary tumor
title Hypoxia-induced nitric oxide release by luminal cells stimulates proliferation and uPA secretion of myoepithelial cells in a bicellular murine mammary tumor
spellingShingle Hypoxia-induced nitric oxide release by luminal cells stimulates proliferation and uPA secretion of myoepithelial cells in a bicellular murine mammary tumor
Krasnapolski, Martin Alejandro
Breast Cancer
Myoepithelial Cells
Hypoxia
Nitric Oxide
Luminal Cells
Migration
title_short Hypoxia-induced nitric oxide release by luminal cells stimulates proliferation and uPA secretion of myoepithelial cells in a bicellular murine mammary tumor
title_full Hypoxia-induced nitric oxide release by luminal cells stimulates proliferation and uPA secretion of myoepithelial cells in a bicellular murine mammary tumor
title_fullStr Hypoxia-induced nitric oxide release by luminal cells stimulates proliferation and uPA secretion of myoepithelial cells in a bicellular murine mammary tumor
title_full_unstemmed Hypoxia-induced nitric oxide release by luminal cells stimulates proliferation and uPA secretion of myoepithelial cells in a bicellular murine mammary tumor
title_sort Hypoxia-induced nitric oxide release by luminal cells stimulates proliferation and uPA secretion of myoepithelial cells in a bicellular murine mammary tumor
dc.creator.none.fl_str_mv Krasnapolski, Martin Alejandro
Lodillinsky, Catalina
Bal, Elisa Dora
Eijan, Ana Maria
author Krasnapolski, Martin Alejandro
author_facet Krasnapolski, Martin Alejandro
Lodillinsky, Catalina
Bal, Elisa Dora
Eijan, Ana Maria
author_role author
author2 Lodillinsky, Catalina
Bal, Elisa Dora
Eijan, Ana Maria
author2_role author
author
author
dc.subject.none.fl_str_mv Breast Cancer
Myoepithelial Cells
Hypoxia
Nitric Oxide
Luminal Cells
Migration
topic Breast Cancer
Myoepithelial Cells
Hypoxia
Nitric Oxide
Luminal Cells
Migration
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Introduction: LM38 murine mammary adenocarcinoma model is formed by LM38-LP (myoepithelial and luminal), LM38-HP (luminal) and LM38-D2 (myoepithelial) cell lines. In a previous work, we had shown that LM38-HP and LM38-D2 cell lines are less malignant than the bicellular LM38-LP cell line. Purpose: To study the role of nitric oxide (NO) as one of the mediators of functional interactions between malignant luminal and myoepithelial cells. Methods and results: Using immunohistochemistry, in vivo iNOS expression was only detected in the luminal cells of bicellular LM38-LP and most cells of LM38-HP tumors. In cobalt-induced pseudohypoxia, LM38-LP and LM38-HP cell lines significantly increased HIF-1α and iNOS expression (Western blotting) and therefore NO production (Griess method). This increase was inhibited by the iNOS inhibitor 1400 W. On the other side, NO was not detectable in LM38-D2 cells either in basal or in pseudohypoxia. In addition, pseudohypoxia increased urokinase-type plasminogen activator (uPA) secretion by LM38-LP and LM38-HP cells and migration in the LM38-LP cell line, without modulating these properties in LM38-D2 cells (radial caseinolysis). The NO donor DETA/NONOate (500 μM) was able to increase uPA secretion and in vitro growth of LM38-D2. In agreement, 1400 W prevented in vivo growth of the myoepithelial LM38-D2 cells. Conclusions: Hypoxia leads to an enhanced NO production by the luminal component, through HIF-1α and iNOS, which can stimulate myoepithelial cell proliferation and uPA secretion. In these new conditions, myoepithelial cells might act as an invasive forefront generating gaps that could help luminal cells to escape from the primary tumor.
Fil: Krasnapolski, Martin Alejandro. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lodillinsky, Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina. Institut Curie Research Center; Francia
Fil: Bal, Elisa Dora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
Fil: Eijan, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
description Introduction: LM38 murine mammary adenocarcinoma model is formed by LM38-LP (myoepithelial and luminal), LM38-HP (luminal) and LM38-D2 (myoepithelial) cell lines. In a previous work, we had shown that LM38-HP and LM38-D2 cell lines are less malignant than the bicellular LM38-LP cell line. Purpose: To study the role of nitric oxide (NO) as one of the mediators of functional interactions between malignant luminal and myoepithelial cells. Methods and results: Using immunohistochemistry, in vivo iNOS expression was only detected in the luminal cells of bicellular LM38-LP and most cells of LM38-HP tumors. In cobalt-induced pseudohypoxia, LM38-LP and LM38-HP cell lines significantly increased HIF-1α and iNOS expression (Western blotting) and therefore NO production (Griess method). This increase was inhibited by the iNOS inhibitor 1400 W. On the other side, NO was not detectable in LM38-D2 cells either in basal or in pseudohypoxia. In addition, pseudohypoxia increased urokinase-type plasminogen activator (uPA) secretion by LM38-LP and LM38-HP cells and migration in the LM38-LP cell line, without modulating these properties in LM38-D2 cells (radial caseinolysis). The NO donor DETA/NONOate (500 μM) was able to increase uPA secretion and in vitro growth of LM38-D2. In agreement, 1400 W prevented in vivo growth of the myoepithelial LM38-D2 cells. Conclusions: Hypoxia leads to an enhanced NO production by the luminal component, through HIF-1α and iNOS, which can stimulate myoepithelial cell proliferation and uPA secretion. In these new conditions, myoepithelial cells might act as an invasive forefront generating gaps that could help luminal cells to escape from the primary tumor.
publishDate 2015
dc.date.none.fl_str_mv 2015-10
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/11336/38864
Krasnapolski, Martin Alejandro; Lodillinsky, Catalina; Bal, Elisa Dora; Eijan, Ana Maria; Hypoxia-induced nitric oxide release by luminal cells stimulates proliferation and uPA secretion of myoepithelial cells in a bicellular murine mammary tumor; Springer Heidelberg; Journal Of Cancer Research And Clinical Oncology; 141; 10; 10-2015; 1727-1738
0171-5216
1432-1335
CONICET Digital
CONICET
url http://hdl.handle.net/11336/38864
identifier_str_mv Krasnapolski, Martin Alejandro; Lodillinsky, Catalina; Bal, Elisa Dora; Eijan, Ana Maria; Hypoxia-induced nitric oxide release by luminal cells stimulates proliferation and uPA secretion of myoepithelial cells in a bicellular murine mammary tumor; Springer Heidelberg; Journal Of Cancer Research And Clinical Oncology; 141; 10; 10-2015; 1727-1738
0171-5216
1432-1335
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1007/s00432-015-1934-1
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00432-015-1934-1
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer Heidelberg
publisher.none.fl_str_mv Springer Heidelberg
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 13.070432

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