SPARC promotes cathepsin B-mediated melanoma invasiveness through a collagen i/α2Β1 integrin axis

Autores
Girotti, Maria Romina; Fernández, Marisol; López, Juan A.; Camafeita, Emilio; Fernandez, Elmer Andres; Albar, Juan P.; Benedetti, Lorena Gabriela; Valacco, Maria Pia; Brekken, Rolf A.; Podhajcer, Osvaldo Luis; Llera, Andrea Sabina
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In melanoma, the extracellular protein SPARC (secreted protein acidic and rich in cysteine) is related to tumor progression. Some of the evidence that links SPARC to melanoma progression indicates that SPARC may be involved in the acquisition of mesenchymal traits that favor metastatic dissemination. However, no molecular pathways that link extracellular SPARC to a mesenchymal phenotype have been described. In this study, global protein expression analysis of the melanoma secretome following enforced downregulation of SPARC expression led us to elucidate a new molecular mechanism by which SPARC promotes cathepsin B-mediated melanoma invasiveness using collagen I and α2β1 integrins as mediators. Interestingly, we also found that the transforming growth factor (TGF)-β1 contribution to cathepsin B-mediated invasion is highly SPARC dependent. In addition, induction of the E-cadherin to N-cadherin switch by SPARC enabled melanoma cells to transmigrate across an endothelial layer through a mechanism independent to that of enhancing invasion. Finally, SPARC also enhanced the extracellular expression of other proteins involved in epithelial–mesenchymal transformation, such as family with sequence similarity 3, member C/interleukin-like EMT-inducer. Our findings demonstrate a previously unreported molecular pathway for SPARC activity on invasion and support an active role of SPARC in the mesenchymal transformation that contributes to melanoma dissemination.
Fil: Girotti, Maria Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Fernández, Marisol. Consejo Superior de Investigaciones Científicas. Centro Nacional de Biotecnología; España
Fil: López, Juan A.. Centro Nacional de Investigaciones Cardiovasculares; España
Fil: Camafeita, Emilio. Centro Nacional de Investigaciones Cardiovasculares; España
Fil: Fernandez, Elmer Andres. Area de Ciencias Agrarias, Ingeniería, Ciencias Biológicas y de la Salud de la Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Albar, Juan P.. Consejo Superior de Investigaciones Científicas. Centro Nacional de Biotecnología; España
Fil: Benedetti, Lorena Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Valacco, Maria Pia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Brekken, Rolf A.. University of Texas; Estados Unidos
Fil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Materia
Cancer
Epithelial to mesenchymal transition
Differential in gel electrophoresis
Secreted protein acidic and rich in cysteine
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:11336/196446
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/196446
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling SPARC promotes cathepsin B-mediated melanoma invasiveness through a collagen i/α2Β1 integrin axisGirotti, Maria RominaFernández, MarisolLópez, Juan A.Camafeita, EmilioFernandez, Elmer AndresAlbar, Juan P.Benedetti, Lorena GabrielaValacco, Maria PiaBrekken, Rolf A.Podhajcer, Osvaldo LuisLlera, Andrea SabinaCancerEpithelial to mesenchymal transitionDifferential in gel electrophoresisSecreted protein acidic and rich in cysteinehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1In melanoma, the extracellular protein SPARC (secreted protein acidic and rich in cysteine) is related to tumor progression. Some of the evidence that links SPARC to melanoma progression indicates that SPARC may be involved in the acquisition of mesenchymal traits that favor metastatic dissemination. However, no molecular pathways that link extracellular SPARC to a mesenchymal phenotype have been described. In this study, global protein expression analysis of the melanoma secretome following enforced downregulation of SPARC expression led us to elucidate a new molecular mechanism by which SPARC promotes cathepsin B-mediated melanoma invasiveness using collagen I and α2β1 integrins as mediators. Interestingly, we also found that the transforming growth factor (TGF)-β1 contribution to cathepsin B-mediated invasion is highly SPARC dependent. In addition, induction of the E-cadherin to N-cadherin switch by SPARC enabled melanoma cells to transmigrate across an endothelial layer through a mechanism independent to that of enhancing invasion. Finally, SPARC also enhanced the extracellular expression of other proteins involved in epithelial–mesenchymal transformation, such as family with sequence similarity 3, member C/interleukin-like EMT-inducer. Our findings demonstrate a previously unreported molecular pathway for SPARC activity on invasion and support an active role of SPARC in the mesenchymal transformation that contributes to melanoma dissemination.Fil: Girotti, Maria Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Fernández, Marisol. Consejo Superior de Investigaciones Científicas. Centro Nacional de Biotecnología; EspañaFil: López, Juan A.. Centro Nacional de Investigaciones Cardiovasculares; EspañaFil: Camafeita, Emilio. Centro Nacional de Investigaciones Cardiovasculares; EspañaFil: Fernandez, Elmer Andres. Area de Ciencias Agrarias, Ingeniería, Ciencias Biológicas y de la Salud de la Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Albar, Juan P.. Consejo Superior de Investigaciones Científicas. Centro Nacional de Biotecnología; EspañaFil: Benedetti, Lorena Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Valacco, Maria Pia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Brekken, Rolf A.. University of Texas; Estados UnidosFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaNature Publishing Group2011-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/196446Girotti, Maria Romina; Fernández, Marisol; López, Juan A.; Camafeita, Emilio; Fernandez, Elmer Andres; et al.; SPARC promotes cathepsin B-mediated melanoma invasiveness through a collagen i/α2Β1 integrin axis; Nature Publishing Group; Journal Of Investigative Dermatology Symposium Proceedings; 131; 8-2011; 2438-24471087-00241529-1774CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/jid.2011.239info:eu-repo/semantics/altIdentifier/url/https://www.jidonline.org/article/S0022-202X(15)35102-2/fulltextinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:07:04Zoai:ri.conicet.gov.ar:11336/196446instacron: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:34982025-10-22 12:07:04.554CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv SPARC promotes cathepsin B-mediated melanoma invasiveness through a collagen i/α2Β1 integrin axis
title SPARC promotes cathepsin B-mediated melanoma invasiveness through a collagen i/α2Β1 integrin axis
spellingShingle SPARC promotes cathepsin B-mediated melanoma invasiveness through a collagen i/α2Β1 integrin axis
Girotti, Maria Romina
Cancer
Epithelial to mesenchymal transition
Differential in gel electrophoresis
Secreted protein acidic and rich in cysteine
title_short SPARC promotes cathepsin B-mediated melanoma invasiveness through a collagen i/α2Β1 integrin axis
title_full SPARC promotes cathepsin B-mediated melanoma invasiveness through a collagen i/α2Β1 integrin axis
title_fullStr SPARC promotes cathepsin B-mediated melanoma invasiveness through a collagen i/α2Β1 integrin axis
title_full_unstemmed SPARC promotes cathepsin B-mediated melanoma invasiveness through a collagen i/α2Β1 integrin axis
title_sort SPARC promotes cathepsin B-mediated melanoma invasiveness through a collagen i/α2Β1 integrin axis
dc.creator.none.fl_str_mv Girotti, Maria Romina
Fernández, Marisol
López, Juan A.
Camafeita, Emilio
Fernandez, Elmer Andres
Albar, Juan P.
Benedetti, Lorena Gabriela
Valacco, Maria Pia
Brekken, Rolf A.
Podhajcer, Osvaldo Luis
Llera, Andrea Sabina
author Girotti, Maria Romina
author_facet Girotti, Maria Romina
Fernández, Marisol
López, Juan A.
Camafeita, Emilio
Fernandez, Elmer Andres
Albar, Juan P.
Benedetti, Lorena Gabriela
Valacco, Maria Pia
Brekken, Rolf A.
Podhajcer, Osvaldo Luis
Llera, Andrea Sabina
author_role author
author2 Fernández, Marisol
López, Juan A.
Camafeita, Emilio
Fernandez, Elmer Andres
Albar, Juan P.
Benedetti, Lorena Gabriela
Valacco, Maria Pia
Brekken, Rolf A.
Podhajcer, Osvaldo Luis
Llera, Andrea Sabina
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cancer
Epithelial to mesenchymal transition
Differential in gel electrophoresis
Secreted protein acidic and rich in cysteine
topic Cancer
Epithelial to mesenchymal transition
Differential in gel electrophoresis
Secreted protein acidic and rich in cysteine
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In melanoma, the extracellular protein SPARC (secreted protein acidic and rich in cysteine) is related to tumor progression. Some of the evidence that links SPARC to melanoma progression indicates that SPARC may be involved in the acquisition of mesenchymal traits that favor metastatic dissemination. However, no molecular pathways that link extracellular SPARC to a mesenchymal phenotype have been described. In this study, global protein expression analysis of the melanoma secretome following enforced downregulation of SPARC expression led us to elucidate a new molecular mechanism by which SPARC promotes cathepsin B-mediated melanoma invasiveness using collagen I and α2β1 integrins as mediators. Interestingly, we also found that the transforming growth factor (TGF)-β1 contribution to cathepsin B-mediated invasion is highly SPARC dependent. In addition, induction of the E-cadherin to N-cadherin switch by SPARC enabled melanoma cells to transmigrate across an endothelial layer through a mechanism independent to that of enhancing invasion. Finally, SPARC also enhanced the extracellular expression of other proteins involved in epithelial–mesenchymal transformation, such as family with sequence similarity 3, member C/interleukin-like EMT-inducer. Our findings demonstrate a previously unreported molecular pathway for SPARC activity on invasion and support an active role of SPARC in the mesenchymal transformation that contributes to melanoma dissemination.
Fil: Girotti, Maria Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Fernández, Marisol. Consejo Superior de Investigaciones Científicas. Centro Nacional de Biotecnología; España
Fil: López, Juan A.. Centro Nacional de Investigaciones Cardiovasculares; España
Fil: Camafeita, Emilio. Centro Nacional de Investigaciones Cardiovasculares; España
Fil: Fernandez, Elmer Andres. Area de Ciencias Agrarias, Ingeniería, Ciencias Biológicas y de la Salud de la Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Albar, Juan P.. Consejo Superior de Investigaciones Científicas. Centro Nacional de Biotecnología; España
Fil: Benedetti, Lorena Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Valacco, Maria Pia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Brekken, Rolf A.. University of Texas; Estados Unidos
Fil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
description In melanoma, the extracellular protein SPARC (secreted protein acidic and rich in cysteine) is related to tumor progression. Some of the evidence that links SPARC to melanoma progression indicates that SPARC may be involved in the acquisition of mesenchymal traits that favor metastatic dissemination. However, no molecular pathways that link extracellular SPARC to a mesenchymal phenotype have been described. In this study, global protein expression analysis of the melanoma secretome following enforced downregulation of SPARC expression led us to elucidate a new molecular mechanism by which SPARC promotes cathepsin B-mediated melanoma invasiveness using collagen I and α2β1 integrins as mediators. Interestingly, we also found that the transforming growth factor (TGF)-β1 contribution to cathepsin B-mediated invasion is highly SPARC dependent. In addition, induction of the E-cadherin to N-cadherin switch by SPARC enabled melanoma cells to transmigrate across an endothelial layer through a mechanism independent to that of enhancing invasion. Finally, SPARC also enhanced the extracellular expression of other proteins involved in epithelial–mesenchymal transformation, such as family with sequence similarity 3, member C/interleukin-like EMT-inducer. Our findings demonstrate a previously unreported molecular pathway for SPARC activity on invasion and support an active role of SPARC in the mesenchymal transformation that contributes to melanoma dissemination.
publishDate 2011
dc.date.none.fl_str_mv 2011-08
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/11336/196446
Girotti, Maria Romina; Fernández, Marisol; López, Juan A.; Camafeita, Emilio; Fernandez, Elmer Andres; et al.; SPARC promotes cathepsin B-mediated melanoma invasiveness through a collagen i/α2Β1 integrin axis; Nature Publishing Group; Journal Of Investigative Dermatology Symposium Proceedings; 131; 8-2011; 2438-2447
1087-0024
1529-1774
CONICET Digital
CONICET
url http://hdl.handle.net/11336/196446
identifier_str_mv Girotti, Maria Romina; Fernández, Marisol; López, Juan A.; Camafeita, Emilio; Fernandez, Elmer Andres; et al.; SPARC promotes cathepsin B-mediated melanoma invasiveness through a collagen i/α2Β1 integrin axis; Nature Publishing Group; Journal Of Investigative Dermatology Symposium Proceedings; 131; 8-2011; 2438-2447
1087-0024
1529-1774
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/jid.2011.239
info:eu-repo/semantics/altIdentifier/url/https://www.jidonline.org/article/S0022-202X(15)35102-2/fulltext
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 Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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 12.982451

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