Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferation

Autores
Aiello, Ignacio; Mul Fedele, Malena Lis; Román, F.; Marpegan, Luciano; Caldart Valle, Carlos Sebastian; Chiesa, Juan José; Golombek, Diego Andrés; Finkielstein, C.V.; Paladino, Natalia
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Circadian disruption negatively affects physiology, posing a global health threat that manifests in proliferative, metabolic, and immune diseases, among others. Because outputs of the circadian clock regulate daily fluctuations in the immune response, we determined whether circadian disruption results in tumor-associated immune cell remodeling, facilitating tumor growth. Our findings show that tumor growth rate increased and latency decreased under circadian disruption conditions compared to normal light-dark (LD) schedules in a murine melanoma model. Circadian disruption induced the loss or inversion of daily patterns of M1 (proinflammatory) and M2 (anti-inflammatory) macrophages and cytokine levels in spleen and tumor tissues. Circadian disruption also induced (i) deregulation of rhythmic expression of clock genes and (ii) of cyclin genes in the liver, (iii) increased CcnA2 levels in the tumor, and (iv) dampened expression of the cell cycle inhibitor p21WAF/CIP1, all of which contribute to a proliferative phenotype.
Fil: Aiello, Ignacio. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Virginia Tech University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mul Fedele, Malena Lis. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Román, F.. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina
Fil: Marpegan, Luciano. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Caldart Valle, Carlos Sebastian. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chiesa, Juan José. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Golombek, Diego Andrés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Finkielstein, C.V.. Virginia Tech University; Estados Unidos
Fil: Paladino, Natalia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
circadian
tumor
immune
cell cycle
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:11336/129668
Acceder
id CONICETDig_3e8bdc88a258d990bca81b4a6e28a31c
oai_identifier_str oai:ri.conicet.gov.ar:11336/129668
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferationAiello, IgnacioMul Fedele, Malena LisRomán, F.Marpegan, LucianoCaldart Valle, Carlos SebastianChiesa, Juan JoséGolombek, Diego AndrésFinkielstein, C.V.Paladino, Nataliacircadiantumorimmunecell cyclehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Circadian disruption negatively affects physiology, posing a global health threat that manifests in proliferative, metabolic, and immune diseases, among others. Because outputs of the circadian clock regulate daily fluctuations in the immune response, we determined whether circadian disruption results in tumor-associated immune cell remodeling, facilitating tumor growth. Our findings show that tumor growth rate increased and latency decreased under circadian disruption conditions compared to normal light-dark (LD) schedules in a murine melanoma model. Circadian disruption induced the loss or inversion of daily patterns of M1 (proinflammatory) and M2 (anti-inflammatory) macrophages and cytokine levels in spleen and tumor tissues. Circadian disruption also induced (i) deregulation of rhythmic expression of clock genes and (ii) of cyclin genes in the liver, (iii) increased CcnA2 levels in the tumor, and (iv) dampened expression of the cell cycle inhibitor p21WAF/CIP1, all of which contribute to a proliferative phenotype.Fil: Aiello, Ignacio. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Virginia Tech University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mul Fedele, Malena Lis. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Román, F.. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Marpegan, Luciano. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Caldart Valle, Carlos Sebastian. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chiesa, Juan José. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andrés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Finkielstein, C.V.. Virginia Tech University; Estados UnidosFil: Paladino, Natalia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaScience Advances is the American Association for the Advancement of Science2020-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/129668Aiello, Ignacio; Mul Fedele, Malena Lis; Román, F.; Marpegan, Luciano; Caldart Valle, Carlos Sebastian; et al.; Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferation; Science Advances is the American Association for the Advancement of Science; Science Advances; 6; 42; 10-2020; 1-132375-2548CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://advances.sciencemag.org/lookup/doi/10.1126/sciadv.aaz4530info:eu-repo/semantics/altIdentifier/doi/10.1126/sciadv.aaz4530info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:02:56Zoai:ri.conicet.gov.ar:11336/129668instacron: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 10:02:56.66CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferation
title Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferation
spellingShingle Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferation
Aiello, Ignacio
circadian
tumor
immune
cell cycle
title_short Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferation
title_full Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferation
title_fullStr Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferation
title_full_unstemmed Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferation
title_sort Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferation
dc.creator.none.fl_str_mv Aiello, Ignacio
Mul Fedele, Malena Lis
Román, F.
Marpegan, Luciano
Caldart Valle, Carlos Sebastian
Chiesa, Juan José
Golombek, Diego Andrés
Finkielstein, C.V.
Paladino, Natalia
author Aiello, Ignacio
author_facet Aiello, Ignacio
Mul Fedele, Malena Lis
Román, F.
Marpegan, Luciano
Caldart Valle, Carlos Sebastian
Chiesa, Juan José
Golombek, Diego Andrés
Finkielstein, C.V.
Paladino, Natalia
author_role author
author2 Mul Fedele, Malena Lis
Román, F.
Marpegan, Luciano
Caldart Valle, Carlos Sebastian
Chiesa, Juan José
Golombek, Diego Andrés
Finkielstein, C.V.
Paladino, Natalia
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv circadian
tumor
immune
cell cycle
topic circadian
tumor
immune
cell cycle
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Circadian disruption negatively affects physiology, posing a global health threat that manifests in proliferative, metabolic, and immune diseases, among others. Because outputs of the circadian clock regulate daily fluctuations in the immune response, we determined whether circadian disruption results in tumor-associated immune cell remodeling, facilitating tumor growth. Our findings show that tumor growth rate increased and latency decreased under circadian disruption conditions compared to normal light-dark (LD) schedules in a murine melanoma model. Circadian disruption induced the loss or inversion of daily patterns of M1 (proinflammatory) and M2 (anti-inflammatory) macrophages and cytokine levels in spleen and tumor tissues. Circadian disruption also induced (i) deregulation of rhythmic expression of clock genes and (ii) of cyclin genes in the liver, (iii) increased CcnA2 levels in the tumor, and (iv) dampened expression of the cell cycle inhibitor p21WAF/CIP1, all of which contribute to a proliferative phenotype.
Fil: Aiello, Ignacio. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Virginia Tech University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mul Fedele, Malena Lis. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Román, F.. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina
Fil: Marpegan, Luciano. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Caldart Valle, Carlos Sebastian. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chiesa, Juan José. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Golombek, Diego Andrés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Finkielstein, C.V.. Virginia Tech University; Estados Unidos
Fil: Paladino, Natalia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Circadian disruption negatively affects physiology, posing a global health threat that manifests in proliferative, metabolic, and immune diseases, among others. Because outputs of the circadian clock regulate daily fluctuations in the immune response, we determined whether circadian disruption results in tumor-associated immune cell remodeling, facilitating tumor growth. Our findings show that tumor growth rate increased and latency decreased under circadian disruption conditions compared to normal light-dark (LD) schedules in a murine melanoma model. Circadian disruption induced the loss or inversion of daily patterns of M1 (proinflammatory) and M2 (anti-inflammatory) macrophages and cytokine levels in spleen and tumor tissues. Circadian disruption also induced (i) deregulation of rhythmic expression of clock genes and (ii) of cyclin genes in the liver, (iii) increased CcnA2 levels in the tumor, and (iv) dampened expression of the cell cycle inhibitor p21WAF/CIP1, all of which contribute to a proliferative phenotype.
publishDate 2020
dc.date.none.fl_str_mv 2020-10
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/11336/129668
Aiello, Ignacio; Mul Fedele, Malena Lis; Román, F.; Marpegan, Luciano; Caldart Valle, Carlos Sebastian; et al.; Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferation; Science Advances is the American Association for the Advancement of Science; Science Advances; 6; 42; 10-2020; 1-13
2375-2548
CONICET Digital
CONICET
url http://hdl.handle.net/11336/129668
identifier_str_mv Aiello, Ignacio; Mul Fedele, Malena Lis; Román, F.; Marpegan, Luciano; Caldart Valle, Carlos Sebastian; et al.; Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferation; Science Advances is the American Association for the Advancement of Science; Science Advances; 6; 42; 10-2020; 1-13
2375-2548
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://advances.sciencemag.org/lookup/doi/10.1126/sciadv.aaz4530
info:eu-repo/semantics/altIdentifier/doi/10.1126/sciadv.aaz4530
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
dc.publisher.none.fl_str_mv Science Advances is the American Association for the Advancement of Science
publisher.none.fl_str_mv Science Advances is the American Association for the Advancement of Science
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
_version_ 1842269776128245760
score 13.13397

Publicaciones similares