Chemo‐small extracellular vesicles released in cisplatin‐resistance ovarian cancer cells are regulated by the lysosomal function

Autores
Cerda Troncoso, Cristóbal; Grünenwald, Felipe; Arias Muñoz, Eloísa; Cavieres, Viviana A.; Caceres Verschae, Albano; Hernández, Sergio; Gaete Ramírez, Belén; Álvarez Astudillo, Francisca; Acuña, Rodrigo A.; Ostrowski, Matias; Burgos, Patricia V.; Varas Godoy, Manuel
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chemoresistance is a common problem in ovarian cancer (OvCa) treatment, where resistant cells, in response to chemotherapy, secrete small extracellular vesicles (sEVs), known as chemo-sEVs, that transfer resistance to recipient cells. sEVs are formed as intraluminal vesicles (ILVs) within multivesicular endosomes (MVEs), whose trafficking is regulated by Ras-associated binding (RAB) GTPases that mediate sEVs secretion or lysosomal degradation. A decrease in lysosomal function can promote sEVs secretion, but the relationship between MVEs trafficking pathways and sEVs secretion in OvCa chemoresistance is unclear. Here, we show that A2780cis cisplatin (CCDP) resistant OvCa cells had an increased number of MVEs and ILVs structures, higher levels of Endosomal Sorting Complex Required for Transport (ESCRTs) machinery components, and RAB27A compared to A2780 CDDP-sensitive OvCa cells. CDDP promoted the secretion of chemo-sEVs in A2780cis cells, enriched in DNA damage response proteins. A2780cis cells exhibited poor lysosomal function with reduced levels of RAB7, essential in MVEs-Lysosomal trafficking. The silencing of RAB27A in A2780cis cells prevents the Chemo-EVs secretion, reduces its chemoresistance and restores lysosomal function and levels of RAB7, switching them into an A2780-like cellular phenotype. Enhancing lysosomal function with rapamycin reduced chemo-sEVs secretion. Our results suggest that adjusting the balance between secretory MVEs and lysosomal MVEs trafficking could be a promising strategy for overcoming CDDP chemoresistance in OvCa.
Fil: Cerda Troncoso, Cristóbal. Universidad San Sebastián; Chile. Fundación Ciencia & Vida; Chile
Fil: Grünenwald, Felipe. Universidad San Sebastián; Chile
Fil: Arias Muñoz, Eloísa. Universidad San Sebastián; Chile
Fil: Cavieres, Viviana A.. Universidad San Sebastián; Chile
Fil: Caceres Verschae, Albano. Universidad San Sebastián; Chile
Fil: Hernández, Sergio. Universidad San Sebastián; Chile
Fil: Gaete Ramírez, Belén. Universidad San Sebastián; Chile
Fil: Álvarez Astudillo, Francisca. Universidad San Sebastián; Chile
Fil: Acuña, Rodrigo A.. Universidad del Desarrollo; Chile
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: Burgos, Patricia V.. Universidad San Sebastián; Chile. Fundación Ciencia & Vida; Chile
Fil: Varas Godoy, Manuel. Universidad San Sebastián; Chile. Fundación Ciencia & Vida; Chile. Advanced Center for Chronic Diseases; Chile
Materia
Vesiculas Extracelulares
Cancer de ovario
Quimioresistencia
Rab27
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/266188
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/266188
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Chemo‐small extracellular vesicles released in cisplatin‐resistance ovarian cancer cells are regulated by the lysosomal functionCerda Troncoso, CristóbalGrünenwald, FelipeArias Muñoz, EloísaCavieres, Viviana A.Caceres Verschae, AlbanoHernández, SergioGaete Ramírez, BelénÁlvarez Astudillo, FranciscaAcuña, Rodrigo A.Ostrowski, MatiasBurgos, Patricia V.Varas Godoy, ManuelVesiculas ExtracelularesCancer de ovarioQuimioresistenciaRab27https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Chemoresistance is a common problem in ovarian cancer (OvCa) treatment, where resistant cells, in response to chemotherapy, secrete small extracellular vesicles (sEVs), known as chemo-sEVs, that transfer resistance to recipient cells. sEVs are formed as intraluminal vesicles (ILVs) within multivesicular endosomes (MVEs), whose trafficking is regulated by Ras-associated binding (RAB) GTPases that mediate sEVs secretion or lysosomal degradation. A decrease in lysosomal function can promote sEVs secretion, but the relationship between MVEs trafficking pathways and sEVs secretion in OvCa chemoresistance is unclear. Here, we show that A2780cis cisplatin (CCDP) resistant OvCa cells had an increased number of MVEs and ILVs structures, higher levels of Endosomal Sorting Complex Required for Transport (ESCRTs) machinery components, and RAB27A compared to A2780 CDDP-sensitive OvCa cells. CDDP promoted the secretion of chemo-sEVs in A2780cis cells, enriched in DNA damage response proteins. A2780cis cells exhibited poor lysosomal function with reduced levels of RAB7, essential in MVEs-Lysosomal trafficking. The silencing of RAB27A in A2780cis cells prevents the Chemo-EVs secretion, reduces its chemoresistance and restores lysosomal function and levels of RAB7, switching them into an A2780-like cellular phenotype. Enhancing lysosomal function with rapamycin reduced chemo-sEVs secretion. Our results suggest that adjusting the balance between secretory MVEs and lysosomal MVEs trafficking could be a promising strategy for overcoming CDDP chemoresistance in OvCa.Fil: Cerda Troncoso, Cristóbal. Universidad San Sebastián; Chile. Fundación Ciencia & Vida; ChileFil: Grünenwald, Felipe. Universidad San Sebastián; ChileFil: Arias Muñoz, Eloísa. Universidad San Sebastián; ChileFil: Cavieres, Viviana A.. Universidad San Sebastián; ChileFil: Caceres Verschae, Albano. Universidad San Sebastián; ChileFil: Hernández, Sergio. Universidad San Sebastián; ChileFil: Gaete Ramírez, Belén. Universidad San Sebastián; ChileFil: Álvarez Astudillo, Francisca. Universidad San Sebastián; ChileFil: Acuña, Rodrigo A.. Universidad del Desarrollo; ChileFil: 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: Burgos, Patricia V.. Universidad San Sebastián; Chile. Fundación Ciencia & Vida; ChileFil: Varas Godoy, Manuel. Universidad San Sebastián; Chile. Fundación Ciencia & Vida; Chile. Advanced Center for Chronic Diseases; ChileWiley Blackwell Publishing, Inc2024-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/266188Cerda Troncoso, Cristóbal; Grünenwald, Felipe; Arias Muñoz, Eloísa; Cavieres, Viviana A.; Caceres Verschae, Albano; et al.; Chemo‐small extracellular vesicles released in cisplatin‐resistance ovarian cancer cells are regulated by the lysosomal function; Wiley Blackwell Publishing, Inc; Journal of Extracellular Biology; 3; 6; 5-2024; 1-262768-2811CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://isevjournals.onlinelibrary.wiley.com/doi/10.1002/jex2.157info:eu-repo/semantics/altIdentifier/doi/10.1002/jex2.157info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:26:35Zoai:ri.conicet.gov.ar:11336/266188instacron: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 10:26:36.23CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Chemo‐small extracellular vesicles released in cisplatin‐resistance ovarian cancer cells are regulated by the lysosomal function
title Chemo‐small extracellular vesicles released in cisplatin‐resistance ovarian cancer cells are regulated by the lysosomal function
spellingShingle Chemo‐small extracellular vesicles released in cisplatin‐resistance ovarian cancer cells are regulated by the lysosomal function
Cerda Troncoso, Cristóbal
Vesiculas Extracelulares
Cancer de ovario
Quimioresistencia
Rab27
title_short Chemo‐small extracellular vesicles released in cisplatin‐resistance ovarian cancer cells are regulated by the lysosomal function
title_full Chemo‐small extracellular vesicles released in cisplatin‐resistance ovarian cancer cells are regulated by the lysosomal function
title_fullStr Chemo‐small extracellular vesicles released in cisplatin‐resistance ovarian cancer cells are regulated by the lysosomal function
title_full_unstemmed Chemo‐small extracellular vesicles released in cisplatin‐resistance ovarian cancer cells are regulated by the lysosomal function
title_sort Chemo‐small extracellular vesicles released in cisplatin‐resistance ovarian cancer cells are regulated by the lysosomal function
dc.creator.none.fl_str_mv Cerda Troncoso, Cristóbal
Grünenwald, Felipe
Arias Muñoz, Eloísa
Cavieres, Viviana A.
Caceres Verschae, Albano
Hernández, Sergio
Gaete Ramírez, Belén
Álvarez Astudillo, Francisca
Acuña, Rodrigo A.
Ostrowski, Matias
Burgos, Patricia V.
Varas Godoy, Manuel
author Cerda Troncoso, Cristóbal
author_facet Cerda Troncoso, Cristóbal
Grünenwald, Felipe
Arias Muñoz, Eloísa
Cavieres, Viviana A.
Caceres Verschae, Albano
Hernández, Sergio
Gaete Ramírez, Belén
Álvarez Astudillo, Francisca
Acuña, Rodrigo A.
Ostrowski, Matias
Burgos, Patricia V.
Varas Godoy, Manuel
author_role author
author2 Grünenwald, Felipe
Arias Muñoz, Eloísa
Cavieres, Viviana A.
Caceres Verschae, Albano
Hernández, Sergio
Gaete Ramírez, Belén
Álvarez Astudillo, Francisca
Acuña, Rodrigo A.
Ostrowski, Matias
Burgos, Patricia V.
Varas Godoy, Manuel
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Vesiculas Extracelulares
Cancer de ovario
Quimioresistencia
Rab27
topic Vesiculas Extracelulares
Cancer de ovario
Quimioresistencia
Rab27
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Chemoresistance is a common problem in ovarian cancer (OvCa) treatment, where resistant cells, in response to chemotherapy, secrete small extracellular vesicles (sEVs), known as chemo-sEVs, that transfer resistance to recipient cells. sEVs are formed as intraluminal vesicles (ILVs) within multivesicular endosomes (MVEs), whose trafficking is regulated by Ras-associated binding (RAB) GTPases that mediate sEVs secretion or lysosomal degradation. A decrease in lysosomal function can promote sEVs secretion, but the relationship between MVEs trafficking pathways and sEVs secretion in OvCa chemoresistance is unclear. Here, we show that A2780cis cisplatin (CCDP) resistant OvCa cells had an increased number of MVEs and ILVs structures, higher levels of Endosomal Sorting Complex Required for Transport (ESCRTs) machinery components, and RAB27A compared to A2780 CDDP-sensitive OvCa cells. CDDP promoted the secretion of chemo-sEVs in A2780cis cells, enriched in DNA damage response proteins. A2780cis cells exhibited poor lysosomal function with reduced levels of RAB7, essential in MVEs-Lysosomal trafficking. The silencing of RAB27A in A2780cis cells prevents the Chemo-EVs secretion, reduces its chemoresistance and restores lysosomal function and levels of RAB7, switching them into an A2780-like cellular phenotype. Enhancing lysosomal function with rapamycin reduced chemo-sEVs secretion. Our results suggest that adjusting the balance between secretory MVEs and lysosomal MVEs trafficking could be a promising strategy for overcoming CDDP chemoresistance in OvCa.
Fil: Cerda Troncoso, Cristóbal. Universidad San Sebastián; Chile. Fundación Ciencia & Vida; Chile
Fil: Grünenwald, Felipe. Universidad San Sebastián; Chile
Fil: Arias Muñoz, Eloísa. Universidad San Sebastián; Chile
Fil: Cavieres, Viviana A.. Universidad San Sebastián; Chile
Fil: Caceres Verschae, Albano. Universidad San Sebastián; Chile
Fil: Hernández, Sergio. Universidad San Sebastián; Chile
Fil: Gaete Ramírez, Belén. Universidad San Sebastián; Chile
Fil: Álvarez Astudillo, Francisca. Universidad San Sebastián; Chile
Fil: Acuña, Rodrigo A.. Universidad del Desarrollo; Chile
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: Burgos, Patricia V.. Universidad San Sebastián; Chile. Fundación Ciencia & Vida; Chile
Fil: Varas Godoy, Manuel. Universidad San Sebastián; Chile. Fundación Ciencia & Vida; Chile. Advanced Center for Chronic Diseases; Chile
description Chemoresistance is a common problem in ovarian cancer (OvCa) treatment, where resistant cells, in response to chemotherapy, secrete small extracellular vesicles (sEVs), known as chemo-sEVs, that transfer resistance to recipient cells. sEVs are formed as intraluminal vesicles (ILVs) within multivesicular endosomes (MVEs), whose trafficking is regulated by Ras-associated binding (RAB) GTPases that mediate sEVs secretion or lysosomal degradation. A decrease in lysosomal function can promote sEVs secretion, but the relationship between MVEs trafficking pathways and sEVs secretion in OvCa chemoresistance is unclear. Here, we show that A2780cis cisplatin (CCDP) resistant OvCa cells had an increased number of MVEs and ILVs structures, higher levels of Endosomal Sorting Complex Required for Transport (ESCRTs) machinery components, and RAB27A compared to A2780 CDDP-sensitive OvCa cells. CDDP promoted the secretion of chemo-sEVs in A2780cis cells, enriched in DNA damage response proteins. A2780cis cells exhibited poor lysosomal function with reduced levels of RAB7, essential in MVEs-Lysosomal trafficking. The silencing of RAB27A in A2780cis cells prevents the Chemo-EVs secretion, reduces its chemoresistance and restores lysosomal function and levels of RAB7, switching them into an A2780-like cellular phenotype. Enhancing lysosomal function with rapamycin reduced chemo-sEVs secretion. Our results suggest that adjusting the balance between secretory MVEs and lysosomal MVEs trafficking could be a promising strategy for overcoming CDDP chemoresistance in OvCa.
publishDate 2024
dc.date.none.fl_str_mv 2024-05
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/11336/266188
Cerda Troncoso, Cristóbal; Grünenwald, Felipe; Arias Muñoz, Eloísa; Cavieres, Viviana A.; Caceres Verschae, Albano; et al.; Chemo‐small extracellular vesicles released in cisplatin‐resistance ovarian cancer cells are regulated by the lysosomal function; Wiley Blackwell Publishing, Inc; Journal of Extracellular Biology; 3; 6; 5-2024; 1-26
2768-2811
CONICET Digital
CONICET
url http://hdl.handle.net/11336/266188
identifier_str_mv Cerda Troncoso, Cristóbal; Grünenwald, Felipe; Arias Muñoz, Eloísa; Cavieres, Viviana A.; Caceres Verschae, Albano; et al.; Chemo‐small extracellular vesicles released in cisplatin‐resistance ovarian cancer cells are regulated by the lysosomal function; Wiley Blackwell Publishing, Inc; Journal of Extracellular Biology; 3; 6; 5-2024; 1-26
2768-2811
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://isevjournals.onlinelibrary.wiley.com/doi/10.1002/jex2.157
info:eu-repo/semantics/altIdentifier/doi/10.1002/jex2.157
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, 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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