Mesenchymal Stromal Cells, CFU-F, From Bone Marrow of untreated Advanced Breast and Lung Cancer Patients Suppress Fibroblast Colonies Formation From Healthy Marrow

Autores
Hofer, Erica Leonor; Labovsky, Vivian; La Russa, Vincent; Fernández Vallone, Valeria Beatriz; Honegger, Alba Elizabeth; Belloc, Carlos Gabriel; Wen, Huei Chi; Bordenave, Raúl Horacio; Bullorsky, Eduardo Oscar; Feldman, Leandro; Chasseing, Norma Alejandra
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We have shown that bone marrow (BM) from untreated advanced lung and breast cancer patients (LCP and BCP) have a reduced number of colony-forming unit fibroblasts (CFU-Fs) or mesenchymal stem cells (MSCs). Factors that regulate the proliferation and differentiation of CFU-F are produced by the patients' BM microenvironment. We have now examined whether conditioned media (CM) from patients' CFU-F-derived stromal cells also inhibits the colony-forming efficiency (CFE) of CFU-F in primary cultures from healthy volunteers (HV)-BM. Thus the number and proliferation potential of HV-CFU-F were also found to be decreased and similar to colony numbers and colony size of patients' CFU-F. Stromal cells from both of these types of colonies appeared relatively larger and lacked the characteristic spindle morphology typically seen in healthy stromal cells. We developed an arbitrary mesenchymal stromal cell maturational index by taking three measures consisting of stromal cell surface area, longitudinal and horizontal axis. All stromal indices derived from HV-CFU-F grown in patients' CM were similar to those from stromal elements derived from patients' CFU-F. These indices were markedly higher than stromal indices typical of HV-CFU-F cultured in healthy CM or standard medium [alpha-medium plus 20% heat-inactivated fetal bovine serum (FBS)]. Patients' CM had increased concentrations of the CFU-F inhibitor, GM-CSF, and low levels of bFGF and Dkk-1, strong promoters of self-renewal of MSCs, compared to the levels quantified in CM from HV-CFU-F. Moreover, the majority of patients' MSCs were unresponsive in standard medium and healthy CM to give CFU-F, indicating that the majority of mesenchymal stromal cells from patients' CFU-F are locked in maturational arrest. These results show that alterations of GM-CSF, bFGF, and Dkk-1 are associated with deficient cloning and maturation arrest of CFU-F. Defective autocrine and paracrine mechanisms may be involved in the BM microenvironments of LCP and BCP.
Fil: Hofer, Erica Leonor. Ministerio de Ciencia, Tecnología e Innovación Productiva. Agencia Nacional de Promoción Cientifíca y Tecnológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
Fil: Labovsky, Vivian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
Fil: La Russa, Vincent. Memorial Sloan-Kettering Cancer Center; Estados Unidos
Fil: Fernández Vallone, Valeria Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
Fil: Honegger, Alba Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
Fil: Belloc, Carlos Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
Fil: Wen, Huei Chi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
Fil: Bordenave, Raúl Horacio. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos "Dr. Isidoro G. Iriarte"; Argentina
Fil: Bullorsky, Eduardo Oscar. Hospital Británico; Argentina
Fil: Feldman, Leandro. Fundacion Favaloro; Argentina
Fil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
Materia
Mesenchymal Stromal Cells
Breast Cancer
Lung Cancer
Cfu-F
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:11336/14685
Acceder
id CONICETDig_82efd2bd17c9142e75a8203619bf80bc
oai_identifier_str oai:ri.conicet.gov.ar:11336/14685
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mesenchymal Stromal Cells, CFU-F, From Bone Marrow of untreated Advanced Breast and Lung Cancer Patients Suppress Fibroblast Colonies Formation From Healthy MarrowHofer, Erica LeonorLabovsky, VivianLa Russa, VincentFernández Vallone, Valeria BeatrizHonegger, Alba ElizabethBelloc, Carlos GabrielWen, Huei ChiBordenave, Raúl HoracioBullorsky, Eduardo OscarFeldman, LeandroChasseing, Norma AlejandraMesenchymal Stromal CellsBreast CancerLung CancerCfu-Fhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3We have shown that bone marrow (BM) from untreated advanced lung and breast cancer patients (LCP and BCP) have a reduced number of colony-forming unit fibroblasts (CFU-Fs) or mesenchymal stem cells (MSCs). Factors that regulate the proliferation and differentiation of CFU-F are produced by the patients' BM microenvironment. We have now examined whether conditioned media (CM) from patients' CFU-F-derived stromal cells also inhibits the colony-forming efficiency (CFE) of CFU-F in primary cultures from healthy volunteers (HV)-BM. Thus the number and proliferation potential of HV-CFU-F were also found to be decreased and similar to colony numbers and colony size of patients' CFU-F. Stromal cells from both of these types of colonies appeared relatively larger and lacked the characteristic spindle morphology typically seen in healthy stromal cells. We developed an arbitrary mesenchymal stromal cell maturational index by taking three measures consisting of stromal cell surface area, longitudinal and horizontal axis. All stromal indices derived from HV-CFU-F grown in patients' CM were similar to those from stromal elements derived from patients' CFU-F. These indices were markedly higher than stromal indices typical of HV-CFU-F cultured in healthy CM or standard medium [alpha-medium plus 20% heat-inactivated fetal bovine serum (FBS)]. Patients' CM had increased concentrations of the CFU-F inhibitor, GM-CSF, and low levels of bFGF and Dkk-1, strong promoters of self-renewal of MSCs, compared to the levels quantified in CM from HV-CFU-F. Moreover, the majority of patients' MSCs were unresponsive in standard medium and healthy CM to give CFU-F, indicating that the majority of mesenchymal stromal cells from patients' CFU-F are locked in maturational arrest. These results show that alterations of GM-CSF, bFGF, and Dkk-1 are associated with deficient cloning and maturation arrest of CFU-F. Defective autocrine and paracrine mechanisms may be involved in the BM microenvironments of LCP and BCP.Fil: Hofer, Erica Leonor. Ministerio de Ciencia, Tecnología e Innovación Productiva. Agencia Nacional de Promoción Cientifíca y Tecnológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Labovsky, Vivian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: La Russa, Vincent. Memorial Sloan-Kettering Cancer Center; Estados UnidosFil: Fernández Vallone, Valeria Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Honegger, Alba Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Belloc, Carlos Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Wen, Huei Chi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Bordenave, Raúl Horacio. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos "Dr. Isidoro G. Iriarte"; ArgentinaFil: Bullorsky, Eduardo Oscar. Hospital Británico; ArgentinaFil: Feldman, Leandro. Fundacion Favaloro; ArgentinaFil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaMary Ann Liebert Inc2010-03-15info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/14685Hofer, Erica Leonor; Labovsky, Vivian; La Russa, Vincent; Fernández Vallone, Valeria Beatriz; Honegger, Alba Elizabeth; et al.; Mesenchymal Stromal Cells, CFU-F, From Bone Marrow of untreated Advanced Breast and Lung Cancer Patients Suppress Fibroblast Colonies Formation From Healthy Marrow; Mary Ann Liebert Inc; Stem Cells And Development; 19; 3; 15-3-2010; 359-3701547-32871557-8534enginfo:eu-repo/semantics/altIdentifier/url/http://online.liebertpub.com/doi/pdfplus/10.1089/scd.2008.0375info:eu-repo/semantics/altIdentifier/doi/10.1089/scd.2008.0375info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:06:33Zoai:ri.conicet.gov.ar:11336/14685instacron: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 10:06:34.198CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mesenchymal Stromal Cells, CFU-F, From Bone Marrow of untreated Advanced Breast and Lung Cancer Patients Suppress Fibroblast Colonies Formation From Healthy Marrow
title Mesenchymal Stromal Cells, CFU-F, From Bone Marrow of untreated Advanced Breast and Lung Cancer Patients Suppress Fibroblast Colonies Formation From Healthy Marrow
spellingShingle Mesenchymal Stromal Cells, CFU-F, From Bone Marrow of untreated Advanced Breast and Lung Cancer Patients Suppress Fibroblast Colonies Formation From Healthy Marrow
Hofer, Erica Leonor
Mesenchymal Stromal Cells
Breast Cancer
Lung Cancer
Cfu-F
title_short Mesenchymal Stromal Cells, CFU-F, From Bone Marrow of untreated Advanced Breast and Lung Cancer Patients Suppress Fibroblast Colonies Formation From Healthy Marrow
title_full Mesenchymal Stromal Cells, CFU-F, From Bone Marrow of untreated Advanced Breast and Lung Cancer Patients Suppress Fibroblast Colonies Formation From Healthy Marrow
title_fullStr Mesenchymal Stromal Cells, CFU-F, From Bone Marrow of untreated Advanced Breast and Lung Cancer Patients Suppress Fibroblast Colonies Formation From Healthy Marrow
title_full_unstemmed Mesenchymal Stromal Cells, CFU-F, From Bone Marrow of untreated Advanced Breast and Lung Cancer Patients Suppress Fibroblast Colonies Formation From Healthy Marrow
title_sort Mesenchymal Stromal Cells, CFU-F, From Bone Marrow of untreated Advanced Breast and Lung Cancer Patients Suppress Fibroblast Colonies Formation From Healthy Marrow
dc.creator.none.fl_str_mv Hofer, Erica Leonor
Labovsky, Vivian
La Russa, Vincent
Fernández Vallone, Valeria Beatriz
Honegger, Alba Elizabeth
Belloc, Carlos Gabriel
Wen, Huei Chi
Bordenave, Raúl Horacio
Bullorsky, Eduardo Oscar
Feldman, Leandro
Chasseing, Norma Alejandra
author Hofer, Erica Leonor
author_facet Hofer, Erica Leonor
Labovsky, Vivian
La Russa, Vincent
Fernández Vallone, Valeria Beatriz
Honegger, Alba Elizabeth
Belloc, Carlos Gabriel
Wen, Huei Chi
Bordenave, Raúl Horacio
Bullorsky, Eduardo Oscar
Feldman, Leandro
Chasseing, Norma Alejandra
author_role author
author2 Labovsky, Vivian
La Russa, Vincent
Fernández Vallone, Valeria Beatriz
Honegger, Alba Elizabeth
Belloc, Carlos Gabriel
Wen, Huei Chi
Bordenave, Raúl Horacio
Bullorsky, Eduardo Oscar
Feldman, Leandro
Chasseing, Norma Alejandra
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Mesenchymal Stromal Cells
Breast Cancer
Lung Cancer
Cfu-F
topic Mesenchymal Stromal Cells
Breast Cancer
Lung Cancer
Cfu-F
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv We have shown that bone marrow (BM) from untreated advanced lung and breast cancer patients (LCP and BCP) have a reduced number of colony-forming unit fibroblasts (CFU-Fs) or mesenchymal stem cells (MSCs). Factors that regulate the proliferation and differentiation of CFU-F are produced by the patients' BM microenvironment. We have now examined whether conditioned media (CM) from patients' CFU-F-derived stromal cells also inhibits the colony-forming efficiency (CFE) of CFU-F in primary cultures from healthy volunteers (HV)-BM. Thus the number and proliferation potential of HV-CFU-F were also found to be decreased and similar to colony numbers and colony size of patients' CFU-F. Stromal cells from both of these types of colonies appeared relatively larger and lacked the characteristic spindle morphology typically seen in healthy stromal cells. We developed an arbitrary mesenchymal stromal cell maturational index by taking three measures consisting of stromal cell surface area, longitudinal and horizontal axis. All stromal indices derived from HV-CFU-F grown in patients' CM were similar to those from stromal elements derived from patients' CFU-F. These indices were markedly higher than stromal indices typical of HV-CFU-F cultured in healthy CM or standard medium [alpha-medium plus 20% heat-inactivated fetal bovine serum (FBS)]. Patients' CM had increased concentrations of the CFU-F inhibitor, GM-CSF, and low levels of bFGF and Dkk-1, strong promoters of self-renewal of MSCs, compared to the levels quantified in CM from HV-CFU-F. Moreover, the majority of patients' MSCs were unresponsive in standard medium and healthy CM to give CFU-F, indicating that the majority of mesenchymal stromal cells from patients' CFU-F are locked in maturational arrest. These results show that alterations of GM-CSF, bFGF, and Dkk-1 are associated with deficient cloning and maturation arrest of CFU-F. Defective autocrine and paracrine mechanisms may be involved in the BM microenvironments of LCP and BCP.
Fil: Hofer, Erica Leonor. Ministerio de Ciencia, Tecnología e Innovación Productiva. Agencia Nacional de Promoción Cientifíca y Tecnológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
Fil: Labovsky, Vivian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
Fil: La Russa, Vincent. Memorial Sloan-Kettering Cancer Center; Estados Unidos
Fil: Fernández Vallone, Valeria Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
Fil: Honegger, Alba Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
Fil: Belloc, Carlos Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
Fil: Wen, Huei Chi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
Fil: Bordenave, Raúl Horacio. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos "Dr. Isidoro G. Iriarte"; Argentina
Fil: Bullorsky, Eduardo Oscar. Hospital Británico; Argentina
Fil: Feldman, Leandro. Fundacion Favaloro; Argentina
Fil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
description We have shown that bone marrow (BM) from untreated advanced lung and breast cancer patients (LCP and BCP) have a reduced number of colony-forming unit fibroblasts (CFU-Fs) or mesenchymal stem cells (MSCs). Factors that regulate the proliferation and differentiation of CFU-F are produced by the patients' BM microenvironment. We have now examined whether conditioned media (CM) from patients' CFU-F-derived stromal cells also inhibits the colony-forming efficiency (CFE) of CFU-F in primary cultures from healthy volunteers (HV)-BM. Thus the number and proliferation potential of HV-CFU-F were also found to be decreased and similar to colony numbers and colony size of patients' CFU-F. Stromal cells from both of these types of colonies appeared relatively larger and lacked the characteristic spindle morphology typically seen in healthy stromal cells. We developed an arbitrary mesenchymal stromal cell maturational index by taking three measures consisting of stromal cell surface area, longitudinal and horizontal axis. All stromal indices derived from HV-CFU-F grown in patients' CM were similar to those from stromal elements derived from patients' CFU-F. These indices were markedly higher than stromal indices typical of HV-CFU-F cultured in healthy CM or standard medium [alpha-medium plus 20% heat-inactivated fetal bovine serum (FBS)]. Patients' CM had increased concentrations of the CFU-F inhibitor, GM-CSF, and low levels of bFGF and Dkk-1, strong promoters of self-renewal of MSCs, compared to the levels quantified in CM from HV-CFU-F. Moreover, the majority of patients' MSCs were unresponsive in standard medium and healthy CM to give CFU-F, indicating that the majority of mesenchymal stromal cells from patients' CFU-F are locked in maturational arrest. These results show that alterations of GM-CSF, bFGF, and Dkk-1 are associated with deficient cloning and maturation arrest of CFU-F. Defective autocrine and paracrine mechanisms may be involved in the BM microenvironments of LCP and BCP.
publishDate 2010
dc.date.none.fl_str_mv 2010-03-15
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/11336/14685
Hofer, Erica Leonor; Labovsky, Vivian; La Russa, Vincent; Fernández Vallone, Valeria Beatriz; Honegger, Alba Elizabeth; et al.; Mesenchymal Stromal Cells, CFU-F, From Bone Marrow of untreated Advanced Breast and Lung Cancer Patients Suppress Fibroblast Colonies Formation From Healthy Marrow; Mary Ann Liebert Inc; Stem Cells And Development; 19; 3; 15-3-2010; 359-370
1547-3287
1557-8534
url http://hdl.handle.net/11336/14685
identifier_str_mv Hofer, Erica Leonor; Labovsky, Vivian; La Russa, Vincent; Fernández Vallone, Valeria Beatriz; Honegger, Alba Elizabeth; et al.; Mesenchymal Stromal Cells, CFU-F, From Bone Marrow of untreated Advanced Breast and Lung Cancer Patients Suppress Fibroblast Colonies Formation From Healthy Marrow; Mary Ann Liebert Inc; Stem Cells And Development; 19; 3; 15-3-2010; 359-370
1547-3287
1557-8534
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://online.liebertpub.com/doi/pdfplus/10.1089/scd.2008.0375
info:eu-repo/semantics/altIdentifier/doi/10.1089/scd.2008.0375
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 Mary Ann Liebert Inc
publisher.none.fl_str_mv Mary Ann Liebert Inc
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 13.070432

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