Senescent mesenchymal stem/stromal cells in pre-metastatic bone marrow of untreated advanced breast cancer patients

Autores
Borzone, Francisco Raúl; Giorello, Maria Belen; Martinez, Leandro Marcelo; Sanmartin, María Cecilia; Feldman, Leonardo; Dimase, Federico; Batagelj, Emilio; Yannarelli, Gustavo Gabriel; Chasseing, Norma Alejandra
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Breast cancer is the predominant form of carcinoma among women worldwide, with 70% of advanced patients developing bone metastases, with a high mortality rate. In this sense, the bone marrow (BM) mesenchymal stem/stromal cells (MSCs) are critical for BM/bone homeostasis, and failures in their functionality, transform the BM into a pre-metastatic niche (PMN). We previously found that BM-MSCs from advanced breast cancer patients (BCPs, infiltrative ductal carcinoma, stage III-B) have an abnormal profile. This work aims to study some of the metabolic and molecular mechanisms underlying MSCs shift from a normal to an abnormal profile in this group of patients. A comparative analysis was undertaken, which included self-renewal capacity, morphology, proliferation capacity, cell cycle, reactive oxygen species (ROS) levels, and senescence-associated β‑galactosidase (SA‑β‑gal) staining of BM-derived MSCs isolated from 14 BCPs and 9 healthy volunteers (HVs). Additionally, the expression and activity of the telomerase subunit TERT, as well as telomere length, were measured. Expression levels of pluripotency, osteogenic, and osteoclastogenic genes (OCT-4, SOX-2, M-CAM, RUNX-2, BMP-2, CCL-2, M-CSF, and IL-6) were also determined. The results showed that MSCs from BCPs had reduced ,self-renewal and proliferation capacity. These cells also exhibited inhibited cell cycle progression and phenotypic changes, such as an enlarged and flattened appearance. Additionally, there was an increase in ROS and senescence levels and a decrease in the functional capacity of TERT to preserve telomere length. We also found an increase in pro-inflammatory/pro-osteoclastogenic gene expression and a decrease in pluripotency gene expression. We conclude that these changes could be responsible for the abnormal functional profile that MSCs show in this group of patients.
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: 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: 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. Weill Cornell Medical College; Estados Unidos
Fil: Sanmartin, María Cecilia. 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. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina
Fil: Feldman, Leonardo. Universidad Nacional del Centro de la Pcia.de Bs.as.. Facultad de Ciencias de la Salud.; Argentina
Fil: Dimase, Federico. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina
Fil: Batagelj, Emilio. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina
Fil: Yannarelli, Gustavo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; 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
MESENCHYMAL STEM CELLS
BONE MARROW
BREAST CANCER
BONE METASTASIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/244696
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/244696
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Senescent mesenchymal stem/stromal cells in pre-metastatic bone marrow of untreated advanced breast cancer patientsBorzone, Francisco RaúlGiorello, Maria BelenMartinez, Leandro MarceloSanmartin, María CeciliaFeldman, LeonardoDimase, FedericoBatagelj, EmilioYannarelli, Gustavo GabrielChasseing, Norma AlejandraMESENCHYMAL STEM CELLSBONE MARROWBREAST CANCERBONE METASTASIShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Breast cancer is the predominant form of carcinoma among women worldwide, with 70% of advanced patients developing bone metastases, with a high mortality rate. In this sense, the bone marrow (BM) mesenchymal stem/stromal cells (MSCs) are critical for BM/bone homeostasis, and failures in their functionality, transform the BM into a pre-metastatic niche (PMN). We previously found that BM-MSCs from advanced breast cancer patients (BCPs, infiltrative ductal carcinoma, stage III-B) have an abnormal profile. This work aims to study some of the metabolic and molecular mechanisms underlying MSCs shift from a normal to an abnormal profile in this group of patients. A comparative analysis was undertaken, which included self-renewal capacity, morphology, proliferation capacity, cell cycle, reactive oxygen species (ROS) levels, and senescence-associated β‑galactosidase (SA‑β‑gal) staining of BM-derived MSCs isolated from 14 BCPs and 9 healthy volunteers (HVs). Additionally, the expression and activity of the telomerase subunit TERT, as well as telomere length, were measured. Expression levels of pluripotency, osteogenic, and osteoclastogenic genes (OCT-4, SOX-2, M-CAM, RUNX-2, BMP-2, CCL-2, M-CSF, and IL-6) were also determined. The results showed that MSCs from BCPs had reduced ,self-renewal and proliferation capacity. These cells also exhibited inhibited cell cycle progression and phenotypic changes, such as an enlarged and flattened appearance. Additionally, there was an increase in ROS and senescence levels and a decrease in the functional capacity of TERT to preserve telomere length. We also found an increase in pro-inflammatory/pro-osteoclastogenic gene expression and a decrease in pluripotency gene expression. We conclude that these changes could be responsible for the abnormal functional profile that MSCs show in this group of patients.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; 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: 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. Weill Cornell Medical College; Estados UnidosFil: Sanmartin, María Cecilia. 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. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Feldman, Leonardo. Universidad Nacional del Centro de la Pcia.de Bs.as.. Facultad de Ciencias de la Salud.; ArgentinaFil: Dimase, Federico. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; ArgentinaFil: Batagelj, Emilio. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; ArgentinaFil: Yannarelli, Gustavo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; 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; ArgentinaCognizant Communication Corp2023-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/244696Borzone, Francisco Raúl; Giorello, Maria Belen; Martinez, Leandro Marcelo; Sanmartin, María Cecilia; Feldman, Leonardo; et al.; Senescent mesenchymal stem/stromal cells in pre-metastatic bone marrow of untreated advanced breast cancer patients; Cognizant Communication Corp; Oncology Research; 31; 3; 3-2023; 361-3740965-0407CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.32604/or.2023.028104info:eu-repo/semantics/altIdentifier/url/https://www.techscience.com/or/v31n3/52818info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:52:26Zoai:ri.conicet.gov.ar:11336/244696instacron: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:34982025-09-03 09:52:26.536CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Senescent mesenchymal stem/stromal cells in pre-metastatic bone marrow of untreated advanced breast cancer patients
title Senescent mesenchymal stem/stromal cells in pre-metastatic bone marrow of untreated advanced breast cancer patients
spellingShingle Senescent mesenchymal stem/stromal cells in pre-metastatic bone marrow of untreated advanced breast cancer patients
Borzone, Francisco Raúl
MESENCHYMAL STEM CELLS
BONE MARROW
BREAST CANCER
BONE METASTASIS
title_short Senescent mesenchymal stem/stromal cells in pre-metastatic bone marrow of untreated advanced breast cancer patients
title_full Senescent mesenchymal stem/stromal cells in pre-metastatic bone marrow of untreated advanced breast cancer patients
title_fullStr Senescent mesenchymal stem/stromal cells in pre-metastatic bone marrow of untreated advanced breast cancer patients
title_full_unstemmed Senescent mesenchymal stem/stromal cells in pre-metastatic bone marrow of untreated advanced breast cancer patients
title_sort Senescent mesenchymal stem/stromal cells in pre-metastatic bone marrow of untreated advanced breast cancer patients
dc.creator.none.fl_str_mv Borzone, Francisco Raúl
Giorello, Maria Belen
Martinez, Leandro Marcelo
Sanmartin, María Cecilia
Feldman, Leonardo
Dimase, Federico
Batagelj, Emilio
Yannarelli, Gustavo Gabriel
Chasseing, Norma Alejandra
author Borzone, Francisco Raúl
author_facet Borzone, Francisco Raúl
Giorello, Maria Belen
Martinez, Leandro Marcelo
Sanmartin, María Cecilia
Feldman, Leonardo
Dimase, Federico
Batagelj, Emilio
Yannarelli, Gustavo Gabriel
Chasseing, Norma Alejandra
author_role author
author2 Giorello, Maria Belen
Martinez, Leandro Marcelo
Sanmartin, María Cecilia
Feldman, Leonardo
Dimase, Federico
Batagelj, Emilio
Yannarelli, Gustavo Gabriel
Chasseing, Norma Alejandra
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv MESENCHYMAL STEM CELLS
BONE MARROW
BREAST CANCER
BONE METASTASIS
topic MESENCHYMAL STEM CELLS
BONE MARROW
BREAST CANCER
BONE METASTASIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Breast cancer is the predominant form of carcinoma among women worldwide, with 70% of advanced patients developing bone metastases, with a high mortality rate. In this sense, the bone marrow (BM) mesenchymal stem/stromal cells (MSCs) are critical for BM/bone homeostasis, and failures in their functionality, transform the BM into a pre-metastatic niche (PMN). We previously found that BM-MSCs from advanced breast cancer patients (BCPs, infiltrative ductal carcinoma, stage III-B) have an abnormal profile. This work aims to study some of the metabolic and molecular mechanisms underlying MSCs shift from a normal to an abnormal profile in this group of patients. A comparative analysis was undertaken, which included self-renewal capacity, morphology, proliferation capacity, cell cycle, reactive oxygen species (ROS) levels, and senescence-associated β‑galactosidase (SA‑β‑gal) staining of BM-derived MSCs isolated from 14 BCPs and 9 healthy volunteers (HVs). Additionally, the expression and activity of the telomerase subunit TERT, as well as telomere length, were measured. Expression levels of pluripotency, osteogenic, and osteoclastogenic genes (OCT-4, SOX-2, M-CAM, RUNX-2, BMP-2, CCL-2, M-CSF, and IL-6) were also determined. The results showed that MSCs from BCPs had reduced ,self-renewal and proliferation capacity. These cells also exhibited inhibited cell cycle progression and phenotypic changes, such as an enlarged and flattened appearance. Additionally, there was an increase in ROS and senescence levels and a decrease in the functional capacity of TERT to preserve telomere length. We also found an increase in pro-inflammatory/pro-osteoclastogenic gene expression and a decrease in pluripotency gene expression. We conclude that these changes could be responsible for the abnormal functional profile that MSCs show in this group of patients.
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: 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: 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. Weill Cornell Medical College; Estados Unidos
Fil: Sanmartin, María Cecilia. 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. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina
Fil: Feldman, Leonardo. Universidad Nacional del Centro de la Pcia.de Bs.as.. Facultad de Ciencias de la Salud.; Argentina
Fil: Dimase, Federico. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina
Fil: Batagelj, Emilio. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina
Fil: Yannarelli, Gustavo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; 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 Breast cancer is the predominant form of carcinoma among women worldwide, with 70% of advanced patients developing bone metastases, with a high mortality rate. In this sense, the bone marrow (BM) mesenchymal stem/stromal cells (MSCs) are critical for BM/bone homeostasis, and failures in their functionality, transform the BM into a pre-metastatic niche (PMN). We previously found that BM-MSCs from advanced breast cancer patients (BCPs, infiltrative ductal carcinoma, stage III-B) have an abnormal profile. This work aims to study some of the metabolic and molecular mechanisms underlying MSCs shift from a normal to an abnormal profile in this group of patients. A comparative analysis was undertaken, which included self-renewal capacity, morphology, proliferation capacity, cell cycle, reactive oxygen species (ROS) levels, and senescence-associated β‑galactosidase (SA‑β‑gal) staining of BM-derived MSCs isolated from 14 BCPs and 9 healthy volunteers (HVs). Additionally, the expression and activity of the telomerase subunit TERT, as well as telomere length, were measured. Expression levels of pluripotency, osteogenic, and osteoclastogenic genes (OCT-4, SOX-2, M-CAM, RUNX-2, BMP-2, CCL-2, M-CSF, and IL-6) were also determined. The results showed that MSCs from BCPs had reduced ,self-renewal and proliferation capacity. These cells also exhibited inhibited cell cycle progression and phenotypic changes, such as an enlarged and flattened appearance. Additionally, there was an increase in ROS and senescence levels and a decrease in the functional capacity of TERT to preserve telomere length. We also found an increase in pro-inflammatory/pro-osteoclastogenic gene expression and a decrease in pluripotency gene expression. We conclude that these changes could be responsible for the abnormal functional profile that MSCs show in this group of patients.
publishDate 2023
dc.date.none.fl_str_mv 2023-03
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/11336/244696
Borzone, Francisco Raúl; Giorello, Maria Belen; Martinez, Leandro Marcelo; Sanmartin, María Cecilia; Feldman, Leonardo; et al.; Senescent mesenchymal stem/stromal cells in pre-metastatic bone marrow of untreated advanced breast cancer patients; Cognizant Communication Corp; Oncology Research; 31; 3; 3-2023; 361-374
0965-0407
CONICET Digital
CONICET
url http://hdl.handle.net/11336/244696
identifier_str_mv Borzone, Francisco Raúl; Giorello, Maria Belen; Martinez, Leandro Marcelo; Sanmartin, María Cecilia; Feldman, Leonardo; et al.; Senescent mesenchymal stem/stromal cells in pre-metastatic bone marrow of untreated advanced breast cancer patients; Cognizant Communication Corp; Oncology Research; 31; 3; 3-2023; 361-374
0965-0407
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.32604/or.2023.028104
info:eu-repo/semantics/altIdentifier/url/https://www.techscience.com/or/v31n3/52818
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cognizant Communication Corp
publisher.none.fl_str_mv Cognizant Communication Corp
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 13.13397

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