Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodeling

Autores
Bravo Miana, Rocío del Carmen; Soler, María Florencia; Ceschin, Danilo Guillermo; Royo, Félix; Negretti Borga, Dana Maria; Azkargorta, Mikel; Elortza, Félix; Montesinos, Maria del Mar; Pellizas, Claudia Gabriela; Falcón-Pérez, Juan Manuel; Donadio, Ana Carolina
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Extracellular vesicles (EVs) participate in cell-stroma crosstalk within the tumor microenvironment and fibroblasts (Fb) contribute to tumor promotion in thyroid cancer. However, the role of tumor-stroma derived EVs still needs to be deciphered. We hypothesized that the interaction of thyroid tumor cells with Fb would liberate EVs with a specific proteomic profile, which would have an impact on EV-functionality in thyroid tumor progression-related events. Tumor (TPC-1, 8505c) and non-tumor (NThyOri) thyroid cells were co-cultured with human Fb. EVs, obtained by ultracentrifugation of conditioned media, were characterized by nanoparticle tracking analysis and western blotting. EV-proteomic analysis was performed by mass-spectrometry, and metalloproteinases (MMPs) were studied by zymography. EV-exchange was evaluated using immunofluorescence, confocal microscopy and FACS. EVs expressed classical exosome markers, with EVs from thyroid tumor cell-Fb co-cultures showing a proteomic profile related to extracellular matrix (ECM) remodeling. Bidirectional crosstalk between Fb and TPC-1 cells produced significantly more EVs than their isolated cells, and potentiated EV-functionality. In line with this, Fb-TPC-1 derived EVs induced MMP2 activation in NThyOri supernatants, and MMP2 activity could be evidenced in Fb and TPC-1 contact-independent co-cultures. Besides, MMP2 interactors allowed us to discriminate between EVs from thyroid tumoral and non-tumoral milieus. Interestingly, Fb internalized more EVs from TPC-1 than from NThyOri producing cells. Fb and thyroid tumor cell crosstalk produces specialized EVs with an ECM remodeling proteomic profile, enabling activation of MMP2 and possibly facilitating ECM-degradation, which is potentially linked with thyroid tumor progression.
Fil: Bravo Miana, Rocío del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba; Argentina
Fil: Soler, María Florencia. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Ceschin, Danilo Guillermo. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Royo, Félix. Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas; España
Fil: Negretti Borga, Dana Maria. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Azkargorta, Mikel. Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas; España
Fil: Elortza, Félix. Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas; España
Fil: Montesinos, Maria del Mar. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Pellizas, Claudia Gabriela. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Falcón-Pérez, Juan Manuel. Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas; España. Ikerbasque, Basque Foundation For Science; España
Fil: Donadio, Ana Carolina. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Materia
CO-CULTURES
EXTRACELLULAR VESICLES
FIBROBLASTS
MMP2
PROTEOMICS
THYROID 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:11336/206378
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/206378
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodelingBravo Miana, Rocío del CarmenSoler, María FlorenciaCeschin, Danilo GuillermoRoyo, FélixNegretti Borga, Dana MariaAzkargorta, MikelElortza, FélixMontesinos, Maria del MarPellizas, Claudia GabrielaFalcón-Pérez, Juan ManuelDonadio, Ana CarolinaCO-CULTURESEXTRACELLULAR VESICLESFIBROBLASTSMMP2PROTEOMICSTHYROID CANCERhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Extracellular vesicles (EVs) participate in cell-stroma crosstalk within the tumor microenvironment and fibroblasts (Fb) contribute to tumor promotion in thyroid cancer. However, the role of tumor-stroma derived EVs still needs to be deciphered. We hypothesized that the interaction of thyroid tumor cells with Fb would liberate EVs with a specific proteomic profile, which would have an impact on EV-functionality in thyroid tumor progression-related events. Tumor (TPC-1, 8505c) and non-tumor (NThyOri) thyroid cells were co-cultured with human Fb. EVs, obtained by ultracentrifugation of conditioned media, were characterized by nanoparticle tracking analysis and western blotting. EV-proteomic analysis was performed by mass-spectrometry, and metalloproteinases (MMPs) were studied by zymography. EV-exchange was evaluated using immunofluorescence, confocal microscopy and FACS. EVs expressed classical exosome markers, with EVs from thyroid tumor cell-Fb co-cultures showing a proteomic profile related to extracellular matrix (ECM) remodeling. Bidirectional crosstalk between Fb and TPC-1 cells produced significantly more EVs than their isolated cells, and potentiated EV-functionality. In line with this, Fb-TPC-1 derived EVs induced MMP2 activation in NThyOri supernatants, and MMP2 activity could be evidenced in Fb and TPC-1 contact-independent co-cultures. Besides, MMP2 interactors allowed us to discriminate between EVs from thyroid tumoral and non-tumoral milieus. Interestingly, Fb internalized more EVs from TPC-1 than from NThyOri producing cells. Fb and thyroid tumor cell crosstalk produces specialized EVs with an ECM remodeling proteomic profile, enabling activation of MMP2 and possibly facilitating ECM-degradation, which is potentially linked with thyroid tumor progression.Fil: Bravo Miana, Rocío del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Soler, María Florencia. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Ceschin, Danilo Guillermo. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Royo, Félix. Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas; EspañaFil: Negretti Borga, Dana Maria. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Azkargorta, Mikel. Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas; EspañaFil: Elortza, Félix. Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas; EspañaFil: Montesinos, Maria del Mar. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Pellizas, Claudia Gabriela. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Falcón-Pérez, Juan Manuel. Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas; España. Ikerbasque, Basque Foundation For Science; EspañaFil: Donadio, Ana Carolina. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaElsevier Gmbh2022-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/206378Bravo Miana, Rocío del Carmen; Soler, María Florencia; Ceschin, Danilo Guillermo; Royo, Félix; Negretti Borga, Dana Maria; et al.; Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodeling; Elsevier Gmbh; European Journal Of Cell Biology; 101; 3; 8-2022; 1-130171-9335CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejcb.2022.151254info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0171933522000577info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:04:46Zoai:ri.conicet.gov.ar:11336/206378instacron: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:34982025-09-10 13:04:46.892CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodeling
title Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodeling
spellingShingle Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodeling
Bravo Miana, Rocío del Carmen
CO-CULTURES
EXTRACELLULAR VESICLES
FIBROBLASTS
MMP2
PROTEOMICS
THYROID CANCER
title_short Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodeling
title_full Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodeling
title_fullStr Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodeling
title_full_unstemmed Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodeling
title_sort Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodeling
dc.creator.none.fl_str_mv Bravo Miana, Rocío del Carmen
Soler, María Florencia
Ceschin, Danilo Guillermo
Royo, Félix
Negretti Borga, Dana Maria
Azkargorta, Mikel
Elortza, Félix
Montesinos, Maria del Mar
Pellizas, Claudia Gabriela
Falcón-Pérez, Juan Manuel
Donadio, Ana Carolina
author Bravo Miana, Rocío del Carmen
author_facet Bravo Miana, Rocío del Carmen
Soler, María Florencia
Ceschin, Danilo Guillermo
Royo, Félix
Negretti Borga, Dana Maria
Azkargorta, Mikel
Elortza, Félix
Montesinos, Maria del Mar
Pellizas, Claudia Gabriela
Falcón-Pérez, Juan Manuel
Donadio, Ana Carolina
author_role author
author2 Soler, María Florencia
Ceschin, Danilo Guillermo
Royo, Félix
Negretti Borga, Dana Maria
Azkargorta, Mikel
Elortza, Félix
Montesinos, Maria del Mar
Pellizas, Claudia Gabriela
Falcón-Pérez, Juan Manuel
Donadio, Ana Carolina
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CO-CULTURES
EXTRACELLULAR VESICLES
FIBROBLASTS
MMP2
PROTEOMICS
THYROID CANCER
topic CO-CULTURES
EXTRACELLULAR VESICLES
FIBROBLASTS
MMP2
PROTEOMICS
THYROID CANCER
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Extracellular vesicles (EVs) participate in cell-stroma crosstalk within the tumor microenvironment and fibroblasts (Fb) contribute to tumor promotion in thyroid cancer. However, the role of tumor-stroma derived EVs still needs to be deciphered. We hypothesized that the interaction of thyroid tumor cells with Fb would liberate EVs with a specific proteomic profile, which would have an impact on EV-functionality in thyroid tumor progression-related events. Tumor (TPC-1, 8505c) and non-tumor (NThyOri) thyroid cells were co-cultured with human Fb. EVs, obtained by ultracentrifugation of conditioned media, were characterized by nanoparticle tracking analysis and western blotting. EV-proteomic analysis was performed by mass-spectrometry, and metalloproteinases (MMPs) were studied by zymography. EV-exchange was evaluated using immunofluorescence, confocal microscopy and FACS. EVs expressed classical exosome markers, with EVs from thyroid tumor cell-Fb co-cultures showing a proteomic profile related to extracellular matrix (ECM) remodeling. Bidirectional crosstalk between Fb and TPC-1 cells produced significantly more EVs than their isolated cells, and potentiated EV-functionality. In line with this, Fb-TPC-1 derived EVs induced MMP2 activation in NThyOri supernatants, and MMP2 activity could be evidenced in Fb and TPC-1 contact-independent co-cultures. Besides, MMP2 interactors allowed us to discriminate between EVs from thyroid tumoral and non-tumoral milieus. Interestingly, Fb internalized more EVs from TPC-1 than from NThyOri producing cells. Fb and thyroid tumor cell crosstalk produces specialized EVs with an ECM remodeling proteomic profile, enabling activation of MMP2 and possibly facilitating ECM-degradation, which is potentially linked with thyroid tumor progression.
Fil: Bravo Miana, Rocío del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba; Argentina
Fil: Soler, María Florencia. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Ceschin, Danilo Guillermo. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Royo, Félix. Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas; España
Fil: Negretti Borga, Dana Maria. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Azkargorta, Mikel. Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas; España
Fil: Elortza, Félix. Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas; España
Fil: Montesinos, Maria del Mar. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Pellizas, Claudia Gabriela. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Falcón-Pérez, Juan Manuel. Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas; España. Ikerbasque, Basque Foundation For Science; España
Fil: Donadio, Ana Carolina. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
description Extracellular vesicles (EVs) participate in cell-stroma crosstalk within the tumor microenvironment and fibroblasts (Fb) contribute to tumor promotion in thyroid cancer. However, the role of tumor-stroma derived EVs still needs to be deciphered. We hypothesized that the interaction of thyroid tumor cells with Fb would liberate EVs with a specific proteomic profile, which would have an impact on EV-functionality in thyroid tumor progression-related events. Tumor (TPC-1, 8505c) and non-tumor (NThyOri) thyroid cells were co-cultured with human Fb. EVs, obtained by ultracentrifugation of conditioned media, were characterized by nanoparticle tracking analysis and western blotting. EV-proteomic analysis was performed by mass-spectrometry, and metalloproteinases (MMPs) were studied by zymography. EV-exchange was evaluated using immunofluorescence, confocal microscopy and FACS. EVs expressed classical exosome markers, with EVs from thyroid tumor cell-Fb co-cultures showing a proteomic profile related to extracellular matrix (ECM) remodeling. Bidirectional crosstalk between Fb and TPC-1 cells produced significantly more EVs than their isolated cells, and potentiated EV-functionality. In line with this, Fb-TPC-1 derived EVs induced MMP2 activation in NThyOri supernatants, and MMP2 activity could be evidenced in Fb and TPC-1 contact-independent co-cultures. Besides, MMP2 interactors allowed us to discriminate between EVs from thyroid tumoral and non-tumoral milieus. Interestingly, Fb internalized more EVs from TPC-1 than from NThyOri producing cells. Fb and thyroid tumor cell crosstalk produces specialized EVs with an ECM remodeling proteomic profile, enabling activation of MMP2 and possibly facilitating ECM-degradation, which is potentially linked with thyroid tumor progression.
publishDate 2022
dc.date.none.fl_str_mv 2022-08
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/11336/206378
Bravo Miana, Rocío del Carmen; Soler, María Florencia; Ceschin, Danilo Guillermo; Royo, Félix; Negretti Borga, Dana Maria; et al.; Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodeling; Elsevier Gmbh; European Journal Of Cell Biology; 101; 3; 8-2022; 1-13
0171-9335
CONICET Digital
CONICET
url http://hdl.handle.net/11336/206378
identifier_str_mv Bravo Miana, Rocío del Carmen; Soler, María Florencia; Ceschin, Danilo Guillermo; Royo, Félix; Negretti Borga, Dana Maria; et al.; Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodeling; Elsevier Gmbh; European Journal Of Cell Biology; 101; 3; 8-2022; 1-13
0171-9335
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejcb.2022.151254
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0171933522000577
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Gmbh
publisher.none.fl_str_mv Elsevier Gmbh
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 12.993085

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