Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer

Autores
Labovsky, Vivian; Martinez, Leandro Marcelo; Calcagno, María de Luján; Davies, Kevin Mauro; Garcia Rivello, Hernan Jorge; Wernicke, Alejandra; Feldman, Leonardo; Giorello, Maria Belen; Matas, Ayelen; Borzone, Francisco Raúl; Howard, Scott C.; Chasseing, Norma Alejandra
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Spindle-shaped stromal cells, like carcinoma-associated fibroblasts and mesenchymal stem cells, influence tumor behavior and can serve as parameters in the clinical diagnosis, therapy, and prognosis of early breast cancer. Therefore, the aim of this study is to explore the clinicopathological significance of tumor necrosis factor-related apoptosis-induced ligand (TRAIL) receptors (Rs) 2 and 4 (TRAIL-R2 and R4), and interleukin-6 R (IL-6R) in spindle-shaped stromal cells, not associated with the vasculature, as prognostic determinants of early breast cancer patients. Receptors are able to trigger the migratory activity, among other functions, of these stromal cells. We conducted immunohistochemical analysis for the expression of these receptors in spindle-shaped stromal cells, not associated with the vasculature, of primary tumors from early invasive breast cancer patients, and analyzed their association with clinicopathological characteristics. Here, we demonstrate that the elevated levels of TRAIL-R2, TRAIL-R4, and IL-6R in these stromal cells were significantly associated with a higher risk of metastatic occurrence (p = 0.034, 0.026, and 0.006; respectively). Moreover, high expression of TRAIL-R4 was associated with shorter disease-free survival and metastasis-free survival (p = 0.013 and 0.019; respectively). Also, high expression of IL-6R was associated with shorter disease-free survival, metastasis-free survival, and overall survival (p = 0.003, 0.001, and 0.003; respectively). Multivariate analysis showed that IL-6R expression was an independent prognostic factor for disease-free survival and metastasis-free survival (p = 0.035). This study is the first to demonstrate that high levels of IL-6R expression in spindle-shaped stromal cells, not associated with the vasculature, could be used to identify early breast cancer patients with poor outcomes.
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: Martinez, Leandro Marcelo. 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: Calcagno, María de Luján. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Davies, Kevin Mauro. Hospital Italiano; Argentina
Fil: Garcia Rivello, Hernan Jorge. Hospital Italiano; Argentina
Fil: Wernicke, Alejandra. Hospital Italiano; Argentina
Fil: Feldman, Leonardo. Fundación Favaloro; Argentina
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: Matas, Ayelen. 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: Howard, Scott C.. University of Memphis; Estados Unidos
Fil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Breast Cancer
Cancer Associated Fibroblasts
Interleukin-6 Receptor
Mesenchymal Stem Cells
Spindle-Shaped Stromal Cells
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:11336/62556
Acceder
id CONICETDig_d25b0789d56a2c22d7ae1c3f9b602119
oai_identifier_str oai:ri.conicet.gov.ar:11336/62556
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancerLabovsky, VivianMartinez, Leandro MarceloCalcagno, María de LujánDavies, Kevin MauroGarcia Rivello, Hernan JorgeWernicke, AlejandraFeldman, LeonardoGiorello, Maria BelenMatas, AyelenBorzone, Francisco RaúlHoward, Scott C.Chasseing, Norma AlejandraBreast CancerCancer Associated FibroblastsInterleukin-6 ReceptorMesenchymal Stem CellsSpindle-Shaped Stromal Cellshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Spindle-shaped stromal cells, like carcinoma-associated fibroblasts and mesenchymal stem cells, influence tumor behavior and can serve as parameters in the clinical diagnosis, therapy, and prognosis of early breast cancer. Therefore, the aim of this study is to explore the clinicopathological significance of tumor necrosis factor-related apoptosis-induced ligand (TRAIL) receptors (Rs) 2 and 4 (TRAIL-R2 and R4), and interleukin-6 R (IL-6R) in spindle-shaped stromal cells, not associated with the vasculature, as prognostic determinants of early breast cancer patients. Receptors are able to trigger the migratory activity, among other functions, of these stromal cells. We conducted immunohistochemical analysis for the expression of these receptors in spindle-shaped stromal cells, not associated with the vasculature, of primary tumors from early invasive breast cancer patients, and analyzed their association with clinicopathological characteristics. Here, we demonstrate that the elevated levels of TRAIL-R2, TRAIL-R4, and IL-6R in these stromal cells were significantly associated with a higher risk of metastatic occurrence (p = 0.034, 0.026, and 0.006; respectively). Moreover, high expression of TRAIL-R4 was associated with shorter disease-free survival and metastasis-free survival (p = 0.013 and 0.019; respectively). Also, high expression of IL-6R was associated with shorter disease-free survival, metastasis-free survival, and overall survival (p = 0.003, 0.001, and 0.003; respectively). Multivariate analysis showed that IL-6R expression was an independent prognostic factor for disease-free survival and metastasis-free survival (p = 0.035). This study is the first to demonstrate that high levels of IL-6R expression in spindle-shaped stromal cells, not associated with the vasculature, could be used to identify early breast cancer patients with poor outcomes.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; ArgentinaFil: Martinez, Leandro Marcelo. 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: Calcagno, María de Luján. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Davies, Kevin Mauro. Hospital Italiano; ArgentinaFil: Garcia Rivello, Hernan Jorge. Hospital Italiano; ArgentinaFil: Wernicke, Alejandra. Hospital Italiano; ArgentinaFil: Feldman, Leonardo. Fundación Favaloro; ArgentinaFil: 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: Matas, Ayelen. 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: Howard, Scott C.. University of Memphis; Estados UnidosFil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaKarger2016-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/62556Labovsky, Vivian; Martinez, Leandro Marcelo; Calcagno, María de Luján; Davies, Kevin Mauro; Garcia Rivello, Hernan Jorge; et al.; Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer; Karger; Tumor Biology; 37; 10; 10-2016; 13377-133841010-4283CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s13277-016-5268-7info:eu-repo/semantics/altIdentifier/doi/10.1007/s13277-016-5268-7info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:01:50Zoai:ri.conicet.gov.ar:11336/62556instacron: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 10:01:51.244CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer
title Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer
spellingShingle Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer
Labovsky, Vivian
Breast Cancer
Cancer Associated Fibroblasts
Interleukin-6 Receptor
Mesenchymal Stem Cells
Spindle-Shaped Stromal Cells
title_short Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer
title_full Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer
title_fullStr Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer
title_full_unstemmed Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer
title_sort Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer
dc.creator.none.fl_str_mv Labovsky, Vivian
Martinez, Leandro Marcelo
Calcagno, María de Luján
Davies, Kevin Mauro
Garcia Rivello, Hernan Jorge
Wernicke, Alejandra
Feldman, Leonardo
Giorello, Maria Belen
Matas, Ayelen
Borzone, Francisco Raúl
Howard, Scott C.
Chasseing, Norma Alejandra
author Labovsky, Vivian
author_facet Labovsky, Vivian
Martinez, Leandro Marcelo
Calcagno, María de Luján
Davies, Kevin Mauro
Garcia Rivello, Hernan Jorge
Wernicke, Alejandra
Feldman, Leonardo
Giorello, Maria Belen
Matas, Ayelen
Borzone, Francisco Raúl
Howard, Scott C.
Chasseing, Norma Alejandra
author_role author
author2 Martinez, Leandro Marcelo
Calcagno, María de Luján
Davies, Kevin Mauro
Garcia Rivello, Hernan Jorge
Wernicke, Alejandra
Feldman, Leonardo
Giorello, Maria Belen
Matas, Ayelen
Borzone, Francisco Raúl
Howard, Scott C.
Chasseing, Norma Alejandra
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Breast Cancer
Cancer Associated Fibroblasts
Interleukin-6 Receptor
Mesenchymal Stem Cells
Spindle-Shaped Stromal Cells
topic Breast Cancer
Cancer Associated Fibroblasts
Interleukin-6 Receptor
Mesenchymal Stem Cells
Spindle-Shaped Stromal Cells
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Spindle-shaped stromal cells, like carcinoma-associated fibroblasts and mesenchymal stem cells, influence tumor behavior and can serve as parameters in the clinical diagnosis, therapy, and prognosis of early breast cancer. Therefore, the aim of this study is to explore the clinicopathological significance of tumor necrosis factor-related apoptosis-induced ligand (TRAIL) receptors (Rs) 2 and 4 (TRAIL-R2 and R4), and interleukin-6 R (IL-6R) in spindle-shaped stromal cells, not associated with the vasculature, as prognostic determinants of early breast cancer patients. Receptors are able to trigger the migratory activity, among other functions, of these stromal cells. We conducted immunohistochemical analysis for the expression of these receptors in spindle-shaped stromal cells, not associated with the vasculature, of primary tumors from early invasive breast cancer patients, and analyzed their association with clinicopathological characteristics. Here, we demonstrate that the elevated levels of TRAIL-R2, TRAIL-R4, and IL-6R in these stromal cells were significantly associated with a higher risk of metastatic occurrence (p = 0.034, 0.026, and 0.006; respectively). Moreover, high expression of TRAIL-R4 was associated with shorter disease-free survival and metastasis-free survival (p = 0.013 and 0.019; respectively). Also, high expression of IL-6R was associated with shorter disease-free survival, metastasis-free survival, and overall survival (p = 0.003, 0.001, and 0.003; respectively). Multivariate analysis showed that IL-6R expression was an independent prognostic factor for disease-free survival and metastasis-free survival (p = 0.035). This study is the first to demonstrate that high levels of IL-6R expression in spindle-shaped stromal cells, not associated with the vasculature, could be used to identify early breast cancer patients with poor outcomes.
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: Martinez, Leandro Marcelo. 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: Calcagno, María de Luján. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Davies, Kevin Mauro. Hospital Italiano; Argentina
Fil: Garcia Rivello, Hernan Jorge. Hospital Italiano; Argentina
Fil: Wernicke, Alejandra. Hospital Italiano; Argentina
Fil: Feldman, Leonardo. Fundación Favaloro; Argentina
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: Matas, Ayelen. 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: Howard, Scott C.. University of Memphis; Estados Unidos
Fil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Spindle-shaped stromal cells, like carcinoma-associated fibroblasts and mesenchymal stem cells, influence tumor behavior and can serve as parameters in the clinical diagnosis, therapy, and prognosis of early breast cancer. Therefore, the aim of this study is to explore the clinicopathological significance of tumor necrosis factor-related apoptosis-induced ligand (TRAIL) receptors (Rs) 2 and 4 (TRAIL-R2 and R4), and interleukin-6 R (IL-6R) in spindle-shaped stromal cells, not associated with the vasculature, as prognostic determinants of early breast cancer patients. Receptors are able to trigger the migratory activity, among other functions, of these stromal cells. We conducted immunohistochemical analysis for the expression of these receptors in spindle-shaped stromal cells, not associated with the vasculature, of primary tumors from early invasive breast cancer patients, and analyzed their association with clinicopathological characteristics. Here, we demonstrate that the elevated levels of TRAIL-R2, TRAIL-R4, and IL-6R in these stromal cells were significantly associated with a higher risk of metastatic occurrence (p = 0.034, 0.026, and 0.006; respectively). Moreover, high expression of TRAIL-R4 was associated with shorter disease-free survival and metastasis-free survival (p = 0.013 and 0.019; respectively). Also, high expression of IL-6R was associated with shorter disease-free survival, metastasis-free survival, and overall survival (p = 0.003, 0.001, and 0.003; respectively). Multivariate analysis showed that IL-6R expression was an independent prognostic factor for disease-free survival and metastasis-free survival (p = 0.035). This study is the first to demonstrate that high levels of IL-6R expression in spindle-shaped stromal cells, not associated with the vasculature, could be used to identify early breast cancer patients with poor outcomes.
publishDate 2016
dc.date.none.fl_str_mv 2016-10
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/11336/62556
Labovsky, Vivian; Martinez, Leandro Marcelo; Calcagno, María de Luján; Davies, Kevin Mauro; Garcia Rivello, Hernan Jorge; et al.; Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer; Karger; Tumor Biology; 37; 10; 10-2016; 13377-13384
1010-4283
CONICET Digital
CONICET
url http://hdl.handle.net/11336/62556
identifier_str_mv Labovsky, Vivian; Martinez, Leandro Marcelo; Calcagno, María de Luján; Davies, Kevin Mauro; Garcia Rivello, Hernan Jorge; et al.; Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer; Karger; Tumor Biology; 37; 10; 10-2016; 13377-13384
1010-4283
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://link.springer.com/article/10.1007/s13277-016-5268-7
info:eu-repo/semantics/altIdentifier/doi/10.1007/s13277-016-5268-7
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
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dc.publisher.none.fl_str_mv Karger
publisher.none.fl_str_mv Karger
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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