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RANK in cancer-associated fibroblasts: A valuable prognostic determinant for metastasis in early-stage breast cancer patients.
Giorello, María Belén; Borzone, Francisco Raúl; Mora, María Florencia; Padin, María Del Rosario; Wernicke, Alejandra; Labovsky, Vivian; Chasseing, Norma Alejandra.
Afiliação
  • Giorello MB; Laboratorio de Inmunohematología, Instituto de Biología y Medicina Experimental (IBYME), Fundación IBYME, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
  • Borzone FR; Laboratorio de Inmunohematología, Instituto de Biología y Medicina Experimental (IBYME), Fundación IBYME, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
  • Mora MF; Departamento de Anatomía Patológica, Hospital Italiano, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
  • Padin MDR; Departamento de Anatomía Patológica, Hospital Italiano, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
  • Wernicke A; Departamento de Anatomía Patológica, Hospital Italiano, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
  • Labovsky V; Laboratorio de Inmunohematología, Instituto de Biología y Medicina Experimental (IBYME), Fundación IBYME, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
  • Chasseing NA; Laboratorio de Inmunohematología, Instituto de Biología y Medicina Experimental (IBYME), Fundación IBYME, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
Cancer Biomark ; 41(2): 115-132, 2024.
Article em En | MEDLINE | ID: mdl-39240628
ABSTRACT

BACKGROUND:

The molecular system of receptor activator of nuclear factor kappa-ß (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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Biomarcadores Tumorais / Receptor Ativador de Fator Nuclear kappa-B / Fibroblastos Associados a Câncer / Estadiamento de Neoplasias Limite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Cancer Biomark Assunto da revista: BIOQUIMICA / NEOPLASIAS Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Argentina País de publicação: Holanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Biomarcadores Tumorais / Receptor Ativador de Fator Nuclear kappa-B / Fibroblastos Associados a Câncer / Estadiamento de Neoplasias Limite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Cancer Biomark Assunto da revista: BIOQUIMICA / NEOPLASIAS Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Argentina País de publicação: Holanda