Osteosarcoma cells relate functionally with stromal cells favoring a lung niche permissive for the establishment of metastatic tumor cells

Autores
Valenzuela Alvarez, Matias Juan Pablo; Gutierrez, Luciana Mariel; Bayo Fina, Juan Miguel; Cantero, María José; García, Mariana Gabriela; Bolontrade, Marcela Fabiana
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Osteosarcoma (OS) is the most common bone tumor and 20% of the patients are diagnosed with metastatic OS at first diagnosis. Undetectable metastases at the time of diagnosis are also a major complication. MSCs display abilities that enable tumor growth. We demonstrated that in vitro, MSCs migrated more towards the secretome of non-metastatic OS cells. When challenged to a secretome from lungs pre-loaded with OS cells, MSCs migrated more towards lungs colonized with metastatic OS cells. Furthermore, MSCs had a preferential migratory and homing behavior in vivo towards lungs´ colonized by metastatic OS cells. In addition, metastatic OS cells showed a higher migratory response towards the MSCs secretome. This feature partnered with increased CTSD expression and release of active MMP2 by metastatic OS cells. We assessed two complementary tumor capabilities relevant to metastatic spread, highlighting the importance of inherent cell features, but also underlining the importance of signaling integration across the niche, suggesting that an interplay of migratory responses between already established OS cells in the lungs, prometastatic OS cells in the primary tumor, and circulating MSCs. Pulmonary metastases remain as a major determinant of OS mortality, and identification of mechanisms and differentially expressed genes would help identify markers and targets for therapeutic approaches of metastatic spread.
Fil: Valenzuela Alvarez, Matias Juan Pablo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; Argentina
Fil: Gutierrez, Luciana Mariel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; Argentina
Fil: Bayo Fina, Juan Miguel. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Cantero, María José. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina
Fil: García, Mariana Gabriela. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina
Fil: Bolontrade, Marcela Fabiana. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; Argentina
Materia
OSTEOSARCOMA
METASTASIS
MEESENCHYMAL STEM CELLS
INVASION
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:11336/255936
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Osteosarcoma cells relate functionally with stromal cells favoring a lung niche permissive for the establishment of metastatic tumor cellsValenzuela Alvarez, Matias Juan PabloGutierrez, Luciana MarielBayo Fina, Juan MiguelCantero, María JoséGarcía, Mariana GabrielaBolontrade, Marcela FabianaOSTEOSARCOMAMETASTASISMEESENCHYMAL STEM CELLSINVASIONhttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Osteosarcoma (OS) is the most common bone tumor and 20% of the patients are diagnosed with metastatic OS at first diagnosis. Undetectable metastases at the time of diagnosis are also a major complication. MSCs display abilities that enable tumor growth. We demonstrated that in vitro, MSCs migrated more towards the secretome of non-metastatic OS cells. When challenged to a secretome from lungs pre-loaded with OS cells, MSCs migrated more towards lungs colonized with metastatic OS cells. Furthermore, MSCs had a preferential migratory and homing behavior in vivo towards lungs´ colonized by metastatic OS cells. In addition, metastatic OS cells showed a higher migratory response towards the MSCs secretome. This feature partnered with increased CTSD expression and release of active MMP2 by metastatic OS cells. We assessed two complementary tumor capabilities relevant to metastatic spread, highlighting the importance of inherent cell features, but also underlining the importance of signaling integration across the niche, suggesting that an interplay of migratory responses between already established OS cells in the lungs, prometastatic OS cells in the primary tumor, and circulating MSCs. Pulmonary metastases remain as a major determinant of OS mortality, and identification of mechanisms and differentially expressed genes would help identify markers and targets for therapeutic approaches of metastatic spread.Fil: Valenzuela Alvarez, Matias Juan Pablo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Gutierrez, Luciana Mariel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Bayo Fina, Juan Miguel. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Cantero, María José. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; ArgentinaFil: García, Mariana Gabriela. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; ArgentinaFil: Bolontrade, Marcela Fabiana. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaResearch Square Company2023-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/255936Valenzuela Alvarez, Matias Juan Pablo; Gutierrez, Luciana Mariel; Bayo Fina, Juan Miguel; Cantero, María José; García, Mariana Gabriela; et al.; Osteosarcoma cells relate functionally with stromal cells favoring a lung niche permissive for the establishment of metastatic tumor cells; Research Square Company; Research Square; 10-2023; 1-172693-5015CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.researchsquare.com/article/rs-3471838/v1info:eu-repo/semantics/altIdentifier/doi/10.21203/rs.3.rs-3471838/v1info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s11033-024-09315-winfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:49:36Zoai:ri.conicet.gov.ar:11336/255936instacron: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:34982025-10-15 14:49:36.338CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Osteosarcoma cells relate functionally with stromal cells favoring a lung niche permissive for the establishment of metastatic tumor cells
title Osteosarcoma cells relate functionally with stromal cells favoring a lung niche permissive for the establishment of metastatic tumor cells
spellingShingle Osteosarcoma cells relate functionally with stromal cells favoring a lung niche permissive for the establishment of metastatic tumor cells
Valenzuela Alvarez, Matias Juan Pablo
OSTEOSARCOMA
METASTASIS
MEESENCHYMAL STEM CELLS
INVASION
title_short Osteosarcoma cells relate functionally with stromal cells favoring a lung niche permissive for the establishment of metastatic tumor cells
title_full Osteosarcoma cells relate functionally with stromal cells favoring a lung niche permissive for the establishment of metastatic tumor cells
title_fullStr Osteosarcoma cells relate functionally with stromal cells favoring a lung niche permissive for the establishment of metastatic tumor cells
title_full_unstemmed Osteosarcoma cells relate functionally with stromal cells favoring a lung niche permissive for the establishment of metastatic tumor cells
title_sort Osteosarcoma cells relate functionally with stromal cells favoring a lung niche permissive for the establishment of metastatic tumor cells
dc.creator.none.fl_str_mv Valenzuela Alvarez, Matias Juan Pablo
Gutierrez, Luciana Mariel
Bayo Fina, Juan Miguel
Cantero, María José
García, Mariana Gabriela
Bolontrade, Marcela Fabiana
author Valenzuela Alvarez, Matias Juan Pablo
author_facet Valenzuela Alvarez, Matias Juan Pablo
Gutierrez, Luciana Mariel
Bayo Fina, Juan Miguel
Cantero, María José
García, Mariana Gabriela
Bolontrade, Marcela Fabiana
author_role author
author2 Gutierrez, Luciana Mariel
Bayo Fina, Juan Miguel
Cantero, María José
García, Mariana Gabriela
Bolontrade, Marcela Fabiana
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv OSTEOSARCOMA
METASTASIS
MEESENCHYMAL STEM CELLS
INVASION
topic OSTEOSARCOMA
METASTASIS
MEESENCHYMAL STEM CELLS
INVASION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Osteosarcoma (OS) is the most common bone tumor and 20% of the patients are diagnosed with metastatic OS at first diagnosis. Undetectable metastases at the time of diagnosis are also a major complication. MSCs display abilities that enable tumor growth. We demonstrated that in vitro, MSCs migrated more towards the secretome of non-metastatic OS cells. When challenged to a secretome from lungs pre-loaded with OS cells, MSCs migrated more towards lungs colonized with metastatic OS cells. Furthermore, MSCs had a preferential migratory and homing behavior in vivo towards lungs´ colonized by metastatic OS cells. In addition, metastatic OS cells showed a higher migratory response towards the MSCs secretome. This feature partnered with increased CTSD expression and release of active MMP2 by metastatic OS cells. We assessed two complementary tumor capabilities relevant to metastatic spread, highlighting the importance of inherent cell features, but also underlining the importance of signaling integration across the niche, suggesting that an interplay of migratory responses between already established OS cells in the lungs, prometastatic OS cells in the primary tumor, and circulating MSCs. Pulmonary metastases remain as a major determinant of OS mortality, and identification of mechanisms and differentially expressed genes would help identify markers and targets for therapeutic approaches of metastatic spread.
Fil: Valenzuela Alvarez, Matias Juan Pablo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; Argentina
Fil: Gutierrez, Luciana Mariel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; Argentina
Fil: Bayo Fina, Juan Miguel. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Cantero, María José. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina
Fil: García, Mariana Gabriela. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina
Fil: Bolontrade, Marcela Fabiana. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; Argentina
description Osteosarcoma (OS) is the most common bone tumor and 20% of the patients are diagnosed with metastatic OS at first diagnosis. Undetectable metastases at the time of diagnosis are also a major complication. MSCs display abilities that enable tumor growth. We demonstrated that in vitro, MSCs migrated more towards the secretome of non-metastatic OS cells. When challenged to a secretome from lungs pre-loaded with OS cells, MSCs migrated more towards lungs colonized with metastatic OS cells. Furthermore, MSCs had a preferential migratory and homing behavior in vivo towards lungs´ colonized by metastatic OS cells. In addition, metastatic OS cells showed a higher migratory response towards the MSCs secretome. This feature partnered with increased CTSD expression and release of active MMP2 by metastatic OS cells. We assessed two complementary tumor capabilities relevant to metastatic spread, highlighting the importance of inherent cell features, but also underlining the importance of signaling integration across the niche, suggesting that an interplay of migratory responses between already established OS cells in the lungs, prometastatic OS cells in the primary tumor, and circulating MSCs. Pulmonary metastases remain as a major determinant of OS mortality, and identification of mechanisms and differentially expressed genes would help identify markers and targets for therapeutic approaches of metastatic spread.
publishDate 2023
dc.date.none.fl_str_mv 2023-10
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/11336/255936
Valenzuela Alvarez, Matias Juan Pablo; Gutierrez, Luciana Mariel; Bayo Fina, Juan Miguel; Cantero, María José; García, Mariana Gabriela; et al.; Osteosarcoma cells relate functionally with stromal cells favoring a lung niche permissive for the establishment of metastatic tumor cells; Research Square Company; Research Square; 10-2023; 1-17
2693-5015
CONICET Digital
CONICET
url http://hdl.handle.net/11336/255936
identifier_str_mv Valenzuela Alvarez, Matias Juan Pablo; Gutierrez, Luciana Mariel; Bayo Fina, Juan Miguel; Cantero, María José; García, Mariana Gabriela; et al.; Osteosarcoma cells relate functionally with stromal cells favoring a lung niche permissive for the establishment of metastatic tumor cells; Research Square Company; Research Square; 10-2023; 1-17
2693-5015
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://www.researchsquare.com/article/rs-3471838/v1
info:eu-repo/semantics/altIdentifier/doi/10.21203/rs.3.rs-3471838/v1
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s11033-024-09315-w
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 Research Square Company
publisher.none.fl_str_mv Research Square Company
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 13.22299

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