Loss of retinal cadherin facilitates mammary tumor progression and metastasis

Autores
Agiostratidou, Georgia; Li, Maomi; Suyama, Kimita; Badano, Ines; Keren, Rinat; Chung, Su; Anzovino, Amy; Hulit, James; Qian, Binzhi; Bouzahzah, Boumediene; Eugenin, Eliseo; Loudig, Olivier; Phillips, Greg R.; Locker, Joseph; Hazan, Rachel B.
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The mammary epithelium is thought to be stabilized by cellcell adhesion mediated mainly by E-cadherin (E-cad). Here, we show that another cadherin, retinal cadherin (R-cad), is critical for maintenance of the epithelial phenotype. R-cad is expressed in nontransformed mammary epithelium but absent from tumorigenic cell lines. In vivo, R-cad was prominently expressed in the epithelium of both ducts and lobules. In human breast cancer, R-cad was down-regulated with tumor progression, with high expression in ductal carcinoma in situ and reduced expression in invasive duct carcinomas. By comparison, E-cad expression persisted in invasive breast tumors and cell lines where R-cad was lost. Consistent with these findings, R-cad knockdown in normal mammary epithelium stimulated invasiveness and disrupted formation of acini despite continued E-cad expression. Conversely, R-cad overexpression in aggressive cell lines induced glandular morphogenesis and inhibited invasiveness, tumor formation, and lung colonization. R-cad also suppressed the matrix metalloproteinase 1 (MMP1), MMP2, and cyclooxygenase 2 gene expression associated with pulmonary metastasis. The data suggest that R-cad is an adhesion molecule of the mammary epithelium, which acts as a critical regulator of the normal phenotype. As a result, R-cad loss contributes to epithelial suppression and metastatic progression. ©2009 American Association for Cancer Research.
Fil: Agiostratidou, Georgia. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Li, Maomi. Albert Einstein College of Medicine, NY; Estados Unidos. Montefiore Medical Center, NY; Estados Unidos
Fil: Suyama, Kimita. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Badano, Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Laboratorio de Biología Molecular Aplicada; Argentina. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Keren, Rinat. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Chung, Su. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Anzovino, Amy. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Hulit, James. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Qian, Binzhi. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Bouzahzah, Boumediene. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Eugenin, Eliseo. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Loudig, Olivier. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Phillips, Greg R.. Mount Sinai School of Medicine, NY; Estados Unidos
Fil: Locker, Joseph. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Hazan, Rachel B.. Albert Einstein College of Medicine, NY; Estados Unidos
Materia
R-Cadherin
Cancer
Metastasis
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:11336/60510
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/60510
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Loss of retinal cadherin facilitates mammary tumor progression and metastasisAgiostratidou, GeorgiaLi, MaomiSuyama, KimitaBadano, InesKeren, RinatChung, SuAnzovino, AmyHulit, JamesQian, BinzhiBouzahzah, BoumedieneEugenin, EliseoLoudig, OlivierPhillips, Greg R.Locker, JosephHazan, Rachel B.R-CadherinCancerMetastasishttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The mammary epithelium is thought to be stabilized by cellcell adhesion mediated mainly by E-cadherin (E-cad). Here, we show that another cadherin, retinal cadherin (R-cad), is critical for maintenance of the epithelial phenotype. R-cad is expressed in nontransformed mammary epithelium but absent from tumorigenic cell lines. In vivo, R-cad was prominently expressed in the epithelium of both ducts and lobules. In human breast cancer, R-cad was down-regulated with tumor progression, with high expression in ductal carcinoma in situ and reduced expression in invasive duct carcinomas. By comparison, E-cad expression persisted in invasive breast tumors and cell lines where R-cad was lost. Consistent with these findings, R-cad knockdown in normal mammary epithelium stimulated invasiveness and disrupted formation of acini despite continued E-cad expression. Conversely, R-cad overexpression in aggressive cell lines induced glandular morphogenesis and inhibited invasiveness, tumor formation, and lung colonization. R-cad also suppressed the matrix metalloproteinase 1 (MMP1), MMP2, and cyclooxygenase 2 gene expression associated with pulmonary metastasis. The data suggest that R-cad is an adhesion molecule of the mammary epithelium, which acts as a critical regulator of the normal phenotype. As a result, R-cad loss contributes to epithelial suppression and metastatic progression. ©2009 American Association for Cancer Research.Fil: Agiostratidou, Georgia. Albert Einstein College of Medicine, NY; Estados UnidosFil: Li, Maomi. Albert Einstein College of Medicine, NY; Estados Unidos. Montefiore Medical Center, NY; Estados UnidosFil: Suyama, Kimita. Albert Einstein College of Medicine, NY; Estados UnidosFil: Badano, Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Laboratorio de Biología Molecular Aplicada; Argentina. Albert Einstein College of Medicine, NY; Estados UnidosFil: Keren, Rinat. Albert Einstein College of Medicine, NY; Estados UnidosFil: Chung, Su. Albert Einstein College of Medicine, NY; Estados UnidosFil: Anzovino, Amy. Albert Einstein College of Medicine, NY; Estados UnidosFil: Hulit, James. Albert Einstein College of Medicine, NY; Estados UnidosFil: Qian, Binzhi. Albert Einstein College of Medicine, NY; Estados UnidosFil: Bouzahzah, Boumediene. Albert Einstein College of Medicine, NY; Estados UnidosFil: Eugenin, Eliseo. Albert Einstein College of Medicine, NY; Estados UnidosFil: Loudig, Olivier. Albert Einstein College of Medicine, NY; Estados UnidosFil: Phillips, Greg R.. Mount Sinai School of Medicine, NY; Estados UnidosFil: Locker, Joseph. Albert Einstein College of Medicine, NY; Estados UnidosFil: Hazan, Rachel B.. Albert Einstein College of Medicine, NY; Estados UnidosAmerican Association for Cancer Research2009-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/60510Agiostratidou, Georgia; Li, Maomi; Suyama, Kimita; Badano, Ines; Keren, Rinat; et al.; Loss of retinal cadherin facilitates mammary tumor progression and metastasis; American Association for Cancer Research; Cancer Research; 69; 12; 6-2009; 5030-50380008-5472CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1158/0008-5472.CAN-08-4007info:eu-repo/semantics/altIdentifier/url/http://cancerres.aacrjournals.org/content/69/12/5030info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:14:17Zoai:ri.conicet.gov.ar:11336/60510instacron: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 10:14:17.465CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Loss of retinal cadherin facilitates mammary tumor progression and metastasis
title Loss of retinal cadherin facilitates mammary tumor progression and metastasis
spellingShingle Loss of retinal cadherin facilitates mammary tumor progression and metastasis
Agiostratidou, Georgia
R-Cadherin
Cancer
Metastasis
title_short Loss of retinal cadherin facilitates mammary tumor progression and metastasis
title_full Loss of retinal cadherin facilitates mammary tumor progression and metastasis
title_fullStr Loss of retinal cadherin facilitates mammary tumor progression and metastasis
title_full_unstemmed Loss of retinal cadherin facilitates mammary tumor progression and metastasis
title_sort Loss of retinal cadherin facilitates mammary tumor progression and metastasis
dc.creator.none.fl_str_mv Agiostratidou, Georgia
Li, Maomi
Suyama, Kimita
Badano, Ines
Keren, Rinat
Chung, Su
Anzovino, Amy
Hulit, James
Qian, Binzhi
Bouzahzah, Boumediene
Eugenin, Eliseo
Loudig, Olivier
Phillips, Greg R.
Locker, Joseph
Hazan, Rachel B.
author Agiostratidou, Georgia
author_facet Agiostratidou, Georgia
Li, Maomi
Suyama, Kimita
Badano, Ines
Keren, Rinat
Chung, Su
Anzovino, Amy
Hulit, James
Qian, Binzhi
Bouzahzah, Boumediene
Eugenin, Eliseo
Loudig, Olivier
Phillips, Greg R.
Locker, Joseph
Hazan, Rachel B.
author_role author
author2 Li, Maomi
Suyama, Kimita
Badano, Ines
Keren, Rinat
Chung, Su
Anzovino, Amy
Hulit, James
Qian, Binzhi
Bouzahzah, Boumediene
Eugenin, Eliseo
Loudig, Olivier
Phillips, Greg R.
Locker, Joseph
Hazan, Rachel B.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv R-Cadherin
Cancer
Metastasis
topic R-Cadherin
Cancer
Metastasis
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The mammary epithelium is thought to be stabilized by cellcell adhesion mediated mainly by E-cadherin (E-cad). Here, we show that another cadherin, retinal cadherin (R-cad), is critical for maintenance of the epithelial phenotype. R-cad is expressed in nontransformed mammary epithelium but absent from tumorigenic cell lines. In vivo, R-cad was prominently expressed in the epithelium of both ducts and lobules. In human breast cancer, R-cad was down-regulated with tumor progression, with high expression in ductal carcinoma in situ and reduced expression in invasive duct carcinomas. By comparison, E-cad expression persisted in invasive breast tumors and cell lines where R-cad was lost. Consistent with these findings, R-cad knockdown in normal mammary epithelium stimulated invasiveness and disrupted formation of acini despite continued E-cad expression. Conversely, R-cad overexpression in aggressive cell lines induced glandular morphogenesis and inhibited invasiveness, tumor formation, and lung colonization. R-cad also suppressed the matrix metalloproteinase 1 (MMP1), MMP2, and cyclooxygenase 2 gene expression associated with pulmonary metastasis. The data suggest that R-cad is an adhesion molecule of the mammary epithelium, which acts as a critical regulator of the normal phenotype. As a result, R-cad loss contributes to epithelial suppression and metastatic progression. ©2009 American Association for Cancer Research.
Fil: Agiostratidou, Georgia. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Li, Maomi. Albert Einstein College of Medicine, NY; Estados Unidos. Montefiore Medical Center, NY; Estados Unidos
Fil: Suyama, Kimita. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Badano, Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Laboratorio de Biología Molecular Aplicada; Argentina. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Keren, Rinat. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Chung, Su. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Anzovino, Amy. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Hulit, James. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Qian, Binzhi. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Bouzahzah, Boumediene. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Eugenin, Eliseo. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Loudig, Olivier. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Phillips, Greg R.. Mount Sinai School of Medicine, NY; Estados Unidos
Fil: Locker, Joseph. Albert Einstein College of Medicine, NY; Estados Unidos
Fil: Hazan, Rachel B.. Albert Einstein College of Medicine, NY; Estados Unidos
description The mammary epithelium is thought to be stabilized by cellcell adhesion mediated mainly by E-cadherin (E-cad). Here, we show that another cadherin, retinal cadherin (R-cad), is critical for maintenance of the epithelial phenotype. R-cad is expressed in nontransformed mammary epithelium but absent from tumorigenic cell lines. In vivo, R-cad was prominently expressed in the epithelium of both ducts and lobules. In human breast cancer, R-cad was down-regulated with tumor progression, with high expression in ductal carcinoma in situ and reduced expression in invasive duct carcinomas. By comparison, E-cad expression persisted in invasive breast tumors and cell lines where R-cad was lost. Consistent with these findings, R-cad knockdown in normal mammary epithelium stimulated invasiveness and disrupted formation of acini despite continued E-cad expression. Conversely, R-cad overexpression in aggressive cell lines induced glandular morphogenesis and inhibited invasiveness, tumor formation, and lung colonization. R-cad also suppressed the matrix metalloproteinase 1 (MMP1), MMP2, and cyclooxygenase 2 gene expression associated with pulmonary metastasis. The data suggest that R-cad is an adhesion molecule of the mammary epithelium, which acts as a critical regulator of the normal phenotype. As a result, R-cad loss contributes to epithelial suppression and metastatic progression. ©2009 American Association for Cancer Research.
publishDate 2009
dc.date.none.fl_str_mv 2009-06
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/11336/60510
Agiostratidou, Georgia; Li, Maomi; Suyama, Kimita; Badano, Ines; Keren, Rinat; et al.; Loss of retinal cadherin facilitates mammary tumor progression and metastasis; American Association for Cancer Research; Cancer Research; 69; 12; 6-2009; 5030-5038
0008-5472
CONICET Digital
CONICET
url http://hdl.handle.net/11336/60510
identifier_str_mv Agiostratidou, Georgia; Li, Maomi; Suyama, Kimita; Badano, Ines; Keren, Rinat; et al.; Loss of retinal cadherin facilitates mammary tumor progression and metastasis; American Association for Cancer Research; Cancer Research; 69; 12; 6-2009; 5030-5038
0008-5472
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1158/0008-5472.CAN-08-4007
info:eu-repo/semantics/altIdentifier/url/http://cancerres.aacrjournals.org/content/69/12/5030
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
dc.publisher.none.fl_str_mv American Association for Cancer Research
publisher.none.fl_str_mv American Association for Cancer Research
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
_version_ 1844614068957085696
score 13.070432

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