Rab27a Supports Exosome-Dependent and -Independent Mechanisms That Modify the Tumor Microenvironment and Can Promote Tumor Progression

Autores
Bobrie, Angélique; Krumeich, Sophie; Reyal, Fabien; Recchi, Chiara; Moita, Luis F.; Seabra, Miguel C.; Ostrowski, Matias; Théry, Clotilde
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
During progression from single cancer cells to a tumor mass and metastases, tumor cells send signals that can subvert their tissue microenvironment. These signals involve soluble molecules and various extracellular vesicles, including a particular type termed exosomes. The specific roles of exosomes secreted in the tumor microenvironment, however, is unclear. The small GTPases RAB27A and RAB27B regulate exocytosis of multivesicular endosomes, which lead to exosome secretion, in human HeLa cells. Here, we used mouse models to show that Rab27a blockade in mammary carcinoma cells decreased secretion of exosomes characterized by endocytic markers, but also of matrix metalloproteinase 9, which is not associated with exosomes. Rab27a blockade resulted in decreased primary tumor growth and lung dissemination of a metastatic carcinoma (4T1), but not of a nonmetastatic carcinoma (TS/A). Local growth of 4T1 tumors required mobilization of a population of neutrophil immune cells induced by Rab27a-dependent secretion of exosomes together with a specific combination of cytokines and/or metalloproteinases. Our findings offer in vivo validation of the concept that exosome secretion can exert key pathophysiologic roles during tumor formation and progression, but they also highlight the idiosyncratic character of the tumor context.
Fil: Bobrie, Angélique. Inserm; Francia. Universite Paris-Descartes; Francia
Fil: Krumeich, Sophie. Inserm; Francia
Fil: Reyal, Fabien. Centre National de la Recherche Scientifique; Francia
Fil: Recchi, Chiara. Imperial College London; Reino Unido
Fil: Moita, Luis F.. Universidade Nova de Lisboa; Portugal
Fil: Seabra, Miguel C.. Imperial College London; Reino Unido. Universidade Nova de Lisboa; Portugal
Fil: Ostrowski, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Théry, Clotilde. Inserm; Francia
Materia
Rab27a
Exosome
Cancer
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:11336/112319
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/112319
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Rab27a Supports Exosome-Dependent and -Independent Mechanisms That Modify the Tumor Microenvironment and Can Promote Tumor ProgressionBobrie, AngéliqueKrumeich, SophieReyal, FabienRecchi, ChiaraMoita, Luis F.Seabra, Miguel C.Ostrowski, MatiasThéry, ClotildeRab27aExosomeCancerhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3During progression from single cancer cells to a tumor mass and metastases, tumor cells send signals that can subvert their tissue microenvironment. These signals involve soluble molecules and various extracellular vesicles, including a particular type termed exosomes. The specific roles of exosomes secreted in the tumor microenvironment, however, is unclear. The small GTPases RAB27A and RAB27B regulate exocytosis of multivesicular endosomes, which lead to exosome secretion, in human HeLa cells. Here, we used mouse models to show that Rab27a blockade in mammary carcinoma cells decreased secretion of exosomes characterized by endocytic markers, but also of matrix metalloproteinase 9, which is not associated with exosomes. Rab27a blockade resulted in decreased primary tumor growth and lung dissemination of a metastatic carcinoma (4T1), but not of a nonmetastatic carcinoma (TS/A). Local growth of 4T1 tumors required mobilization of a population of neutrophil immune cells induced by Rab27a-dependent secretion of exosomes together with a specific combination of cytokines and/or metalloproteinases. Our findings offer in vivo validation of the concept that exosome secretion can exert key pathophysiologic roles during tumor formation and progression, but they also highlight the idiosyncratic character of the tumor context.Fil: Bobrie, Angélique. Inserm; Francia. Universite Paris-Descartes; FranciaFil: Krumeich, Sophie. Inserm; FranciaFil: Reyal, Fabien. Centre National de la Recherche Scientifique; FranciaFil: Recchi, Chiara. Imperial College London; Reino UnidoFil: Moita, Luis F.. Universidade Nova de Lisboa; PortugalFil: Seabra, Miguel C.. Imperial College London; Reino Unido. Universidade Nova de Lisboa; PortugalFil: Ostrowski, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Théry, Clotilde. Inserm; FranciaAmerican Association for Cancer Research2012-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/112319Bobrie, Angélique; Krumeich, Sophie; Reyal, Fabien; Recchi, Chiara; Moita, Luis F.; et al.; Rab27a Supports Exosome-Dependent and -Independent Mechanisms That Modify the Tumor Microenvironment and Can Promote Tumor Progression; American Association for Cancer Research; Cancer Research; 72; 19; 10-2012; 4920-49300008-5472CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://cancerres.aacrjournals.org/content/72/19/4920info:eu-repo/semantics/altIdentifier/doi/10.1158/0008-5472.CAN-12-0925info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:05:47Zoai:ri.conicet.gov.ar:11336/112319instacron: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 10:05:47.694CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Rab27a Supports Exosome-Dependent and -Independent Mechanisms That Modify the Tumor Microenvironment and Can Promote Tumor Progression
title Rab27a Supports Exosome-Dependent and -Independent Mechanisms That Modify the Tumor Microenvironment and Can Promote Tumor Progression
spellingShingle Rab27a Supports Exosome-Dependent and -Independent Mechanisms That Modify the Tumor Microenvironment and Can Promote Tumor Progression
Bobrie, Angélique
Rab27a
Exosome
Cancer
title_short Rab27a Supports Exosome-Dependent and -Independent Mechanisms That Modify the Tumor Microenvironment and Can Promote Tumor Progression
title_full Rab27a Supports Exosome-Dependent and -Independent Mechanisms That Modify the Tumor Microenvironment and Can Promote Tumor Progression
title_fullStr Rab27a Supports Exosome-Dependent and -Independent Mechanisms That Modify the Tumor Microenvironment and Can Promote Tumor Progression
title_full_unstemmed Rab27a Supports Exosome-Dependent and -Independent Mechanisms That Modify the Tumor Microenvironment and Can Promote Tumor Progression
title_sort Rab27a Supports Exosome-Dependent and -Independent Mechanisms That Modify the Tumor Microenvironment and Can Promote Tumor Progression
dc.creator.none.fl_str_mv Bobrie, Angélique
Krumeich, Sophie
Reyal, Fabien
Recchi, Chiara
Moita, Luis F.
Seabra, Miguel C.
Ostrowski, Matias
Théry, Clotilde
author Bobrie, Angélique
author_facet Bobrie, Angélique
Krumeich, Sophie
Reyal, Fabien
Recchi, Chiara
Moita, Luis F.
Seabra, Miguel C.
Ostrowski, Matias
Théry, Clotilde
author_role author
author2 Krumeich, Sophie
Reyal, Fabien
Recchi, Chiara
Moita, Luis F.
Seabra, Miguel C.
Ostrowski, Matias
Théry, Clotilde
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Rab27a
Exosome
Cancer
topic Rab27a
Exosome
Cancer
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv During progression from single cancer cells to a tumor mass and metastases, tumor cells send signals that can subvert their tissue microenvironment. These signals involve soluble molecules and various extracellular vesicles, including a particular type termed exosomes. The specific roles of exosomes secreted in the tumor microenvironment, however, is unclear. The small GTPases RAB27A and RAB27B regulate exocytosis of multivesicular endosomes, which lead to exosome secretion, in human HeLa cells. Here, we used mouse models to show that Rab27a blockade in mammary carcinoma cells decreased secretion of exosomes characterized by endocytic markers, but also of matrix metalloproteinase 9, which is not associated with exosomes. Rab27a blockade resulted in decreased primary tumor growth and lung dissemination of a metastatic carcinoma (4T1), but not of a nonmetastatic carcinoma (TS/A). Local growth of 4T1 tumors required mobilization of a population of neutrophil immune cells induced by Rab27a-dependent secretion of exosomes together with a specific combination of cytokines and/or metalloproteinases. Our findings offer in vivo validation of the concept that exosome secretion can exert key pathophysiologic roles during tumor formation and progression, but they also highlight the idiosyncratic character of the tumor context.
Fil: Bobrie, Angélique. Inserm; Francia. Universite Paris-Descartes; Francia
Fil: Krumeich, Sophie. Inserm; Francia
Fil: Reyal, Fabien. Centre National de la Recherche Scientifique; Francia
Fil: Recchi, Chiara. Imperial College London; Reino Unido
Fil: Moita, Luis F.. Universidade Nova de Lisboa; Portugal
Fil: Seabra, Miguel C.. Imperial College London; Reino Unido. Universidade Nova de Lisboa; Portugal
Fil: Ostrowski, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Théry, Clotilde. Inserm; Francia
description During progression from single cancer cells to a tumor mass and metastases, tumor cells send signals that can subvert their tissue microenvironment. These signals involve soluble molecules and various extracellular vesicles, including a particular type termed exosomes. The specific roles of exosomes secreted in the tumor microenvironment, however, is unclear. The small GTPases RAB27A and RAB27B regulate exocytosis of multivesicular endosomes, which lead to exosome secretion, in human HeLa cells. Here, we used mouse models to show that Rab27a blockade in mammary carcinoma cells decreased secretion of exosomes characterized by endocytic markers, but also of matrix metalloproteinase 9, which is not associated with exosomes. Rab27a blockade resulted in decreased primary tumor growth and lung dissemination of a metastatic carcinoma (4T1), but not of a nonmetastatic carcinoma (TS/A). Local growth of 4T1 tumors required mobilization of a population of neutrophil immune cells induced by Rab27a-dependent secretion of exosomes together with a specific combination of cytokines and/or metalloproteinases. Our findings offer in vivo validation of the concept that exosome secretion can exert key pathophysiologic roles during tumor formation and progression, but they also highlight the idiosyncratic character of the tumor context.
publishDate 2012
dc.date.none.fl_str_mv 2012-10
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/11336/112319
Bobrie, Angélique; Krumeich, Sophie; Reyal, Fabien; Recchi, Chiara; Moita, Luis F.; et al.; Rab27a Supports Exosome-Dependent and -Independent Mechanisms That Modify the Tumor Microenvironment and Can Promote Tumor Progression; American Association for Cancer Research; Cancer Research; 72; 19; 10-2012; 4920-4930
0008-5472
CONICET Digital
CONICET
url http://hdl.handle.net/11336/112319
identifier_str_mv Bobrie, Angélique; Krumeich, Sophie; Reyal, Fabien; Recchi, Chiara; Moita, Luis F.; et al.; Rab27a Supports Exosome-Dependent and -Independent Mechanisms That Modify the Tumor Microenvironment and Can Promote Tumor Progression; American Association for Cancer Research; Cancer Research; 72; 19; 10-2012; 4920-4930
0008-5472
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://cancerres.aacrjournals.org/content/72/19/4920
info:eu-repo/semantics/altIdentifier/doi/10.1158/0008-5472.CAN-12-0925
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 American Association for Cancer Research
publisher.none.fl_str_mv American Association for Cancer Research
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_ 1842269928787279872
score 13.13397

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