RANK in cancer-associated fibroblasts: A valuable prognostic determinant for metastasis in early-stage breast cancer patients

Autores
Giorello, Maria Belen; Borzone, Francisco Raúl; Mora, María Florencia; Padin, María del Rosario; Wernicke, Alejandra; Labovsky, Vivian; Chasseing, Norma Alejandra
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BACKGROUND: The molecular system of receptor activator of nuclear factor kappa-β (RANK) and its ligand (RANKL) plays a role in a variety of physiological and pathological processes. These encompass the regulation of bone metabolism, mammary gland development, immune function, as well as their involvement and tumorigenesis. Nevertheless, limited knowledge exists regarding their function within the tumor microenvironment. METHODS AND RESULTS: We explored the significance of RANK expression in cancer-associated fibroblasts (CAFs) as a prognostic biomarker in early breast cancer patients (BCPs) by immunohistochemistry. Results reveal a significant correlation between high RANK expression in CAFs and an increased risk of metastasis (p = 0.006), shorter metastasis-free survival (MFS) [p = 0.007, OR (95%CI) = 2.290 (1.259–4.156)], and lower overall survival (OS) [p = 0.004, OR (95%CI) = 2.469 (1.343– 4.541)]. Upon analyzing the phenotype of CD34(-) CAFs isolated from primary tumors in BCPs, we observed co-expression of RANK with CD105 marker by immunofluorescence and flow cytometry, characteristic of mesenchymal stem/stromal cells (MSCs), suggesting the possible cellular origin. Also RANKL-RANK system increase the OCT-4, SOX-2 and DKK-1 (dickkopf 1) gene expression in CD34(-) CAFs by RT-PCR. Moreover, this system plays a crucial role in the migration of these CD34(-) CAFs. CONCLUSIONS: These results support the clinical relevance of RANK in CAFs and propose its potential as a future therapeutic target in the treatment of early BCPs.
Fil: Giorello, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Borzone, Francisco Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Mora, María Florencia. Hospital Italiano; Argentina
Fil: Padin, María del Rosario. Hospital Italiano; Argentina
Fil: Wernicke, Alejandra. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Labovsky, Vivian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
RANK RECEPTOR
CANCER-ASSOCIATED FIBROBLASTS
BREAST CANCER
RANKL-RANK SYSTEM
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/261456
Acceder
id CONICETDig_45f3b2a3b48df9df549d456703917f56
oai_identifier_str oai:ri.conicet.gov.ar:11336/261456
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling RANK in cancer-associated fibroblasts: A valuable prognostic determinant for metastasis in early-stage breast cancer patientsGiorello, Maria BelenBorzone, Francisco RaúlMora, María FlorenciaPadin, María del RosarioWernicke, AlejandraLabovsky, VivianChasseing, Norma AlejandraRANK RECEPTORCANCER-ASSOCIATED FIBROBLASTSBREAST CANCERRANKL-RANK SYSTEMhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3BACKGROUND: The molecular system of receptor activator of nuclear factor kappa-β (RANK) and its ligand (RANKL) plays a role in a variety of physiological and pathological processes. These encompass the regulation of bone metabolism, mammary gland development, immune function, as well as their involvement and tumorigenesis. Nevertheless, limited knowledge exists regarding their function within the tumor microenvironment. METHODS AND RESULTS: We explored the significance of RANK expression in cancer-associated fibroblasts (CAFs) as a prognostic biomarker in early breast cancer patients (BCPs) by immunohistochemistry. Results reveal a significant correlation between high RANK expression in CAFs and an increased risk of metastasis (p = 0.006), shorter metastasis-free survival (MFS) [p = 0.007, OR (95%CI) = 2.290 (1.259–4.156)], and lower overall survival (OS) [p = 0.004, OR (95%CI) = 2.469 (1.343– 4.541)]. Upon analyzing the phenotype of CD34(-) CAFs isolated from primary tumors in BCPs, we observed co-expression of RANK with CD105 marker by immunofluorescence and flow cytometry, characteristic of mesenchymal stem/stromal cells (MSCs), suggesting the possible cellular origin. Also RANKL-RANK system increase the OCT-4, SOX-2 and DKK-1 (dickkopf 1) gene expression in CD34(-) CAFs by RT-PCR. Moreover, this system plays a crucial role in the migration of these CD34(-) CAFs. CONCLUSIONS: These results support the clinical relevance of RANK in CAFs and propose its potential as a future therapeutic target in the treatment of early BCPs.Fil: Giorello, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Borzone, Francisco Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Mora, María Florencia. Hospital Italiano; ArgentinaFil: Padin, María del Rosario. Hospital Italiano; ArgentinaFil: Wernicke, Alejandra. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Labovsky, Vivian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaIOS Press2024-10info: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/11336/261456Giorello, Maria Belen; Borzone, Francisco Raúl; Mora, María Florencia; Padin, María del Rosario; Wernicke, Alejandra; et al.; RANK in cancer-associated fibroblasts: A valuable prognostic determinant for metastasis in early-stage breast cancer patients; IOS Press; Cancer Biomarkers; 41; 2; 10-2024; 115-1321574-0153CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.sagepub.com/doi/10.3233/CBM-230523info:eu-repo/semantics/altIdentifier/doi/10.3233/CBM-230523info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:23:22Zoai:ri.conicet.gov.ar:11336/261456instacron: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:34982025-09-10 13:23:23.268CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv RANK in cancer-associated fibroblasts: A valuable prognostic determinant for metastasis in early-stage breast cancer patients
title RANK in cancer-associated fibroblasts: A valuable prognostic determinant for metastasis in early-stage breast cancer patients
spellingShingle RANK in cancer-associated fibroblasts: A valuable prognostic determinant for metastasis in early-stage breast cancer patients
Giorello, Maria Belen
RANK RECEPTOR
CANCER-ASSOCIATED FIBROBLASTS
BREAST CANCER
RANKL-RANK SYSTEM
title_short RANK in cancer-associated fibroblasts: A valuable prognostic determinant for metastasis in early-stage breast cancer patients
title_full RANK in cancer-associated fibroblasts: A valuable prognostic determinant for metastasis in early-stage breast cancer patients
title_fullStr RANK in cancer-associated fibroblasts: A valuable prognostic determinant for metastasis in early-stage breast cancer patients
title_full_unstemmed RANK in cancer-associated fibroblasts: A valuable prognostic determinant for metastasis in early-stage breast cancer patients
title_sort RANK in cancer-associated fibroblasts: A valuable prognostic determinant for metastasis in early-stage breast cancer patients
dc.creator.none.fl_str_mv Giorello, Maria Belen
Borzone, Francisco Raúl
Mora, María Florencia
Padin, María del Rosario
Wernicke, Alejandra
Labovsky, Vivian
Chasseing, Norma Alejandra
author Giorello, Maria Belen
author_facet Giorello, Maria Belen
Borzone, Francisco Raúl
Mora, María Florencia
Padin, María del Rosario
Wernicke, Alejandra
Labovsky, Vivian
Chasseing, Norma Alejandra
author_role author
author2 Borzone, Francisco Raúl
Mora, María Florencia
Padin, María del Rosario
Wernicke, Alejandra
Labovsky, Vivian
Chasseing, Norma Alejandra
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv RANK RECEPTOR
CANCER-ASSOCIATED FIBROBLASTS
BREAST CANCER
RANKL-RANK SYSTEM
topic RANK RECEPTOR
CANCER-ASSOCIATED FIBROBLASTS
BREAST CANCER
RANKL-RANK SYSTEM
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv BACKGROUND: The molecular system of receptor activator of nuclear factor kappa-β (RANK) and its ligand (RANKL) plays a role in a variety of physiological and pathological processes. These encompass the regulation of bone metabolism, mammary gland development, immune function, as well as their involvement and tumorigenesis. Nevertheless, limited knowledge exists regarding their function within the tumor microenvironment. METHODS AND RESULTS: We explored the significance of RANK expression in cancer-associated fibroblasts (CAFs) as a prognostic biomarker in early breast cancer patients (BCPs) by immunohistochemistry. Results reveal a significant correlation between high RANK expression in CAFs and an increased risk of metastasis (p = 0.006), shorter metastasis-free survival (MFS) [p = 0.007, OR (95%CI) = 2.290 (1.259–4.156)], and lower overall survival (OS) [p = 0.004, OR (95%CI) = 2.469 (1.343– 4.541)]. Upon analyzing the phenotype of CD34(-) CAFs isolated from primary tumors in BCPs, we observed co-expression of RANK with CD105 marker by immunofluorescence and flow cytometry, characteristic of mesenchymal stem/stromal cells (MSCs), suggesting the possible cellular origin. Also RANKL-RANK system increase the OCT-4, SOX-2 and DKK-1 (dickkopf 1) gene expression in CD34(-) CAFs by RT-PCR. Moreover, this system plays a crucial role in the migration of these CD34(-) CAFs. CONCLUSIONS: These results support the clinical relevance of RANK in CAFs and propose its potential as a future therapeutic target in the treatment of early BCPs.
Fil: Giorello, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Borzone, Francisco Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Mora, María Florencia. Hospital Italiano; Argentina
Fil: Padin, María del Rosario. Hospital Italiano; Argentina
Fil: Wernicke, Alejandra. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Labovsky, Vivian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description BACKGROUND: The molecular system of receptor activator of nuclear factor kappa-β (RANK) and its ligand (RANKL) plays a role in a variety of physiological and pathological processes. These encompass the regulation of bone metabolism, mammary gland development, immune function, as well as their involvement and tumorigenesis. Nevertheless, limited knowledge exists regarding their function within the tumor microenvironment. METHODS AND RESULTS: We explored the significance of RANK expression in cancer-associated fibroblasts (CAFs) as a prognostic biomarker in early breast cancer patients (BCPs) by immunohistochemistry. Results reveal a significant correlation between high RANK expression in CAFs and an increased risk of metastasis (p = 0.006), shorter metastasis-free survival (MFS) [p = 0.007, OR (95%CI) = 2.290 (1.259–4.156)], and lower overall survival (OS) [p = 0.004, OR (95%CI) = 2.469 (1.343– 4.541)]. Upon analyzing the phenotype of CD34(-) CAFs isolated from primary tumors in BCPs, we observed co-expression of RANK with CD105 marker by immunofluorescence and flow cytometry, characteristic of mesenchymal stem/stromal cells (MSCs), suggesting the possible cellular origin. Also RANKL-RANK system increase the OCT-4, SOX-2 and DKK-1 (dickkopf 1) gene expression in CD34(-) CAFs by RT-PCR. Moreover, this system plays a crucial role in the migration of these CD34(-) CAFs. CONCLUSIONS: These results support the clinical relevance of RANK in CAFs and propose its potential as a future therapeutic target in the treatment of early BCPs.
publishDate 2024
dc.date.none.fl_str_mv 2024-10
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/11336/261456
Giorello, Maria Belen; Borzone, Francisco Raúl; Mora, María Florencia; Padin, María del Rosario; Wernicke, Alejandra; et al.; RANK in cancer-associated fibroblasts: A valuable prognostic determinant for metastasis in early-stage breast cancer patients; IOS Press; Cancer Biomarkers; 41; 2; 10-2024; 115-132
1574-0153
CONICET Digital
CONICET
url http://hdl.handle.net/11336/261456
identifier_str_mv Giorello, Maria Belen; Borzone, Francisco Raúl; Mora, María Florencia; Padin, María del Rosario; Wernicke, Alejandra; et al.; RANK in cancer-associated fibroblasts: A valuable prognostic determinant for metastasis in early-stage breast cancer patients; IOS Press; Cancer Biomarkers; 41; 2; 10-2024; 115-132
1574-0153
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://journals.sagepub.com/doi/10.3233/CBM-230523
info:eu-repo/semantics/altIdentifier/doi/10.3233/CBM-230523
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv IOS Press
publisher.none.fl_str_mv IOS Press
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 12.48226

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