SPARC is a new driver of early breast tumor progression via TGF-β -dependent mechanism

Autores
Sciacca, Marianela; Carballo, Pilar; Lacunza, Ezequiel; Marino, Lina; Cardozo, Noelia Paola; Lopez Lopez, Tamara; Abba, Martín Carlos; Courtois, Laura; Bieche, Ivan; Vincent Salomon, Anne; Rojas Bilbao, Erica; Podsypanina, Katrina; Boissan, Mathieu; Chavrier, Philippe; Eijan, Ana Maria; Saez, Pablo J.; Lodillinsky, Catalina
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Ductal carcinoma in situ (DCIS) is a pre-invasive lesion that is thought to be a precursor of invasive ductal carcinoma (IDC). The challenge lies in discriminating between DCIS progressors and DCIS non-progressors, often resulting in over- or under-treatment in many cases. Membrane type 1 (MT1)-matrix metalloproteinase (MMP) has been previously identified as an essential gene involved in DCIS progression. Here, RNA-sequencing analysis of MT1-MMPhigh subpopulation derived from invasive breast tumors in the intraductal xenograft model was compared against a dataset of human high-grade DCIS, and Secreted Protein Acidic and Cysteine Rich (SPARC) has emerged as a master candidate involved in early breast tumor progression. We report that SPARC is up-regulated in DCIS as compared to normal breast epithelial tissues, and further increased in IDC relative to synchronous DCIS foci. We found a positive correlation between SPARC and MT1-MMP expression in DCIS lesions. At the mechanistic level, depletion of SPARC reduced MT1-MMP expression, the degradative capacity of the cells and the activation of the TGF-β signalling canonical pathway. Pharmacological inhibition of the TGF-β signalling pathway decreased SPARC and MT1-MMP at the mRNA and protein level, and concomitantly the cell degradative capacity and 3D cell migration. Strikingly, inhibition of the TGF-β signalling pathway limits the invasive transition of breast tumors in a new triple-negative mouse intraductal syngeneic xenograft model. Moreover, high SPARC expression was positively correlated with both, TGF-β and its receptor, TGFBRI, in a basal type of breast cancer collection supporting our findings. This study identifies SPARC as a new driver of early breast tumor progression via a TGF-β-dependent mechanism, suggesting TGF-β signaling pathway as a potential target for patients with high SPARC expression.
Fil: Sciacca, Marianela. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Carballo, Pilar. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Lacunza, Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Marino, Lina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Cardozo, Noelia Paola. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Lopez Lopez, Tamara. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Courtois, Laura. Institut Curie; Francia
Fil: Bieche, Ivan. Institut Curie; Francia
Fil: Vincent Salomon, Anne. Institut Curie; Francia
Fil: Rojas Bilbao, Erica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Podsypanina, Katrina. Institut Curie; Francia
Fil: Boissan, Mathieu. Centre de Recherche Saint Antoine; Francia
Fil: Chavrier, Philippe. Institut Curie; Francia
Fil: Eijan, Ana Maria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Saez, Pablo J.. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Lodillinsky, Catalina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
SPARC
BREAST CANCER
DCIS
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:11336/272772
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling SPARC is a new driver of early breast tumor progression via TGF-β -dependent mechanismSciacca, MarianelaCarballo, PilarLacunza, EzequielMarino, LinaCardozo, Noelia PaolaLopez Lopez, TamaraAbba, Martín CarlosCourtois, LauraBieche, IvanVincent Salomon, AnneRojas Bilbao, EricaPodsypanina, KatrinaBoissan, MathieuChavrier, PhilippeEijan, Ana MariaSaez, Pablo J.Lodillinsky, CatalinaSPARCBREAST CANCERDCIShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Ductal carcinoma in situ (DCIS) is a pre-invasive lesion that is thought to be a precursor of invasive ductal carcinoma (IDC). The challenge lies in discriminating between DCIS progressors and DCIS non-progressors, often resulting in over- or under-treatment in many cases. Membrane type 1 (MT1)-matrix metalloproteinase (MMP) has been previously identified as an essential gene involved in DCIS progression. Here, RNA-sequencing analysis of MT1-MMPhigh subpopulation derived from invasive breast tumors in the intraductal xenograft model was compared against a dataset of human high-grade DCIS, and Secreted Protein Acidic and Cysteine Rich (SPARC) has emerged as a master candidate involved in early breast tumor progression. We report that SPARC is up-regulated in DCIS as compared to normal breast epithelial tissues, and further increased in IDC relative to synchronous DCIS foci. We found a positive correlation between SPARC and MT1-MMP expression in DCIS lesions. At the mechanistic level, depletion of SPARC reduced MT1-MMP expression, the degradative capacity of the cells and the activation of the TGF-β signalling canonical pathway. Pharmacological inhibition of the TGF-β signalling pathway decreased SPARC and MT1-MMP at the mRNA and protein level, and concomitantly the cell degradative capacity and 3D cell migration. Strikingly, inhibition of the TGF-β signalling pathway limits the invasive transition of breast tumors in a new triple-negative mouse intraductal syngeneic xenograft model. Moreover, high SPARC expression was positively correlated with both, TGF-β and its receptor, TGFBRI, in a basal type of breast cancer collection supporting our findings. This study identifies SPARC as a new driver of early breast tumor progression via a TGF-β-dependent mechanism, suggesting TGF-β signaling pathway as a potential target for patients with high SPARC expression.Fil: Sciacca, Marianela. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carballo, Pilar. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Lacunza, Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Marino, Lina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Cardozo, Noelia Paola. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Lopez Lopez, Tamara. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Courtois, Laura. Institut Curie; FranciaFil: Bieche, Ivan. Institut Curie; FranciaFil: Vincent Salomon, Anne. Institut Curie; FranciaFil: Rojas Bilbao, Erica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Podsypanina, Katrina. Institut Curie; FranciaFil: Boissan, Mathieu. Centre de Recherche Saint Antoine; FranciaFil: Chavrier, Philippe. Institut Curie; FranciaFil: Eijan, Ana Maria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Saez, Pablo J.. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Lodillinsky, Catalina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaCold Spring Harbor Laboratory Press2025-01info: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/11336/272772Sciacca, Marianela; Carballo, Pilar; Lacunza, Ezequiel; Marino, Lina; Cardozo, Noelia Paola; et al.; SPARC is a new driver of early breast tumor progression via TGF-β -dependent mechanism; Cold Spring Harbor Laboratory Press; bioRxiv.org; 2025; 1-2025; 1-342692-8205CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1101/2025.01.17.632337info:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2025.01.17.632337v1info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:49:41Zoai:ri.conicet.gov.ar:11336/272772instacron: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:34982025-10-15 14:49:42.024CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv SPARC is a new driver of early breast tumor progression via TGF-β -dependent mechanism
title SPARC is a new driver of early breast tumor progression via TGF-β -dependent mechanism
spellingShingle SPARC is a new driver of early breast tumor progression via TGF-β -dependent mechanism
Sciacca, Marianela
SPARC
BREAST CANCER
DCIS
title_short SPARC is a new driver of early breast tumor progression via TGF-β -dependent mechanism
title_full SPARC is a new driver of early breast tumor progression via TGF-β -dependent mechanism
title_fullStr SPARC is a new driver of early breast tumor progression via TGF-β -dependent mechanism
title_full_unstemmed SPARC is a new driver of early breast tumor progression via TGF-β -dependent mechanism
title_sort SPARC is a new driver of early breast tumor progression via TGF-β -dependent mechanism
dc.creator.none.fl_str_mv Sciacca, Marianela
Carballo, Pilar
Lacunza, Ezequiel
Marino, Lina
Cardozo, Noelia Paola
Lopez Lopez, Tamara
Abba, Martín Carlos
Courtois, Laura
Bieche, Ivan
Vincent Salomon, Anne
Rojas Bilbao, Erica
Podsypanina, Katrina
Boissan, Mathieu
Chavrier, Philippe
Eijan, Ana Maria
Saez, Pablo J.
Lodillinsky, Catalina
author Sciacca, Marianela
author_facet Sciacca, Marianela
Carballo, Pilar
Lacunza, Ezequiel
Marino, Lina
Cardozo, Noelia Paola
Lopez Lopez, Tamara
Abba, Martín Carlos
Courtois, Laura
Bieche, Ivan
Vincent Salomon, Anne
Rojas Bilbao, Erica
Podsypanina, Katrina
Boissan, Mathieu
Chavrier, Philippe
Eijan, Ana Maria
Saez, Pablo J.
Lodillinsky, Catalina
author_role author
author2 Carballo, Pilar
Lacunza, Ezequiel
Marino, Lina
Cardozo, Noelia Paola
Lopez Lopez, Tamara
Abba, Martín Carlos
Courtois, Laura
Bieche, Ivan
Vincent Salomon, Anne
Rojas Bilbao, Erica
Podsypanina, Katrina
Boissan, Mathieu
Chavrier, Philippe
Eijan, Ana Maria
Saez, Pablo J.
Lodillinsky, Catalina
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv SPARC
BREAST CANCER
DCIS
topic SPARC
BREAST CANCER
DCIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Ductal carcinoma in situ (DCIS) is a pre-invasive lesion that is thought to be a precursor of invasive ductal carcinoma (IDC). The challenge lies in discriminating between DCIS progressors and DCIS non-progressors, often resulting in over- or under-treatment in many cases. Membrane type 1 (MT1)-matrix metalloproteinase (MMP) has been previously identified as an essential gene involved in DCIS progression. Here, RNA-sequencing analysis of MT1-MMPhigh subpopulation derived from invasive breast tumors in the intraductal xenograft model was compared against a dataset of human high-grade DCIS, and Secreted Protein Acidic and Cysteine Rich (SPARC) has emerged as a master candidate involved in early breast tumor progression. We report that SPARC is up-regulated in DCIS as compared to normal breast epithelial tissues, and further increased in IDC relative to synchronous DCIS foci. We found a positive correlation between SPARC and MT1-MMP expression in DCIS lesions. At the mechanistic level, depletion of SPARC reduced MT1-MMP expression, the degradative capacity of the cells and the activation of the TGF-β signalling canonical pathway. Pharmacological inhibition of the TGF-β signalling pathway decreased SPARC and MT1-MMP at the mRNA and protein level, and concomitantly the cell degradative capacity and 3D cell migration. Strikingly, inhibition of the TGF-β signalling pathway limits the invasive transition of breast tumors in a new triple-negative mouse intraductal syngeneic xenograft model. Moreover, high SPARC expression was positively correlated with both, TGF-β and its receptor, TGFBRI, in a basal type of breast cancer collection supporting our findings. This study identifies SPARC as a new driver of early breast tumor progression via a TGF-β-dependent mechanism, suggesting TGF-β signaling pathway as a potential target for patients with high SPARC expression.
Fil: Sciacca, Marianela. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Carballo, Pilar. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Lacunza, Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Marino, Lina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Cardozo, Noelia Paola. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Lopez Lopez, Tamara. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Courtois, Laura. Institut Curie; Francia
Fil: Bieche, Ivan. Institut Curie; Francia
Fil: Vincent Salomon, Anne. Institut Curie; Francia
Fil: Rojas Bilbao, Erica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Podsypanina, Katrina. Institut Curie; Francia
Fil: Boissan, Mathieu. Centre de Recherche Saint Antoine; Francia
Fil: Chavrier, Philippe. Institut Curie; Francia
Fil: Eijan, Ana Maria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Saez, Pablo J.. University Medical Center Hamburg-Eppendorf; Alemania
Fil: Lodillinsky, Catalina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Ductal carcinoma in situ (DCIS) is a pre-invasive lesion that is thought to be a precursor of invasive ductal carcinoma (IDC). The challenge lies in discriminating between DCIS progressors and DCIS non-progressors, often resulting in over- or under-treatment in many cases. Membrane type 1 (MT1)-matrix metalloproteinase (MMP) has been previously identified as an essential gene involved in DCIS progression. Here, RNA-sequencing analysis of MT1-MMPhigh subpopulation derived from invasive breast tumors in the intraductal xenograft model was compared against a dataset of human high-grade DCIS, and Secreted Protein Acidic and Cysteine Rich (SPARC) has emerged as a master candidate involved in early breast tumor progression. We report that SPARC is up-regulated in DCIS as compared to normal breast epithelial tissues, and further increased in IDC relative to synchronous DCIS foci. We found a positive correlation between SPARC and MT1-MMP expression in DCIS lesions. At the mechanistic level, depletion of SPARC reduced MT1-MMP expression, the degradative capacity of the cells and the activation of the TGF-β signalling canonical pathway. Pharmacological inhibition of the TGF-β signalling pathway decreased SPARC and MT1-MMP at the mRNA and protein level, and concomitantly the cell degradative capacity and 3D cell migration. Strikingly, inhibition of the TGF-β signalling pathway limits the invasive transition of breast tumors in a new triple-negative mouse intraductal syngeneic xenograft model. Moreover, high SPARC expression was positively correlated with both, TGF-β and its receptor, TGFBRI, in a basal type of breast cancer collection supporting our findings. This study identifies SPARC as a new driver of early breast tumor progression via a TGF-β-dependent mechanism, suggesting TGF-β signaling pathway as a potential target for patients with high SPARC expression.
publishDate 2025
dc.date.none.fl_str_mv 2025-01
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/11336/272772
Sciacca, Marianela; Carballo, Pilar; Lacunza, Ezequiel; Marino, Lina; Cardozo, Noelia Paola; et al.; SPARC is a new driver of early breast tumor progression via TGF-β -dependent mechanism; Cold Spring Harbor Laboratory Press; bioRxiv.org; 2025; 1-2025; 1-34
2692-8205
CONICET Digital
CONICET
url http://hdl.handle.net/11336/272772
identifier_str_mv Sciacca, Marianela; Carballo, Pilar; Lacunza, Ezequiel; Marino, Lina; Cardozo, Noelia Paola; et al.; SPARC is a new driver of early breast tumor progression via TGF-β -dependent mechanism; Cold Spring Harbor Laboratory Press; bioRxiv.org; 2025; 1-2025; 1-34
2692-8205
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1101/2025.01.17.632337
info:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2025.01.17.632337v1
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 Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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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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