Ovarian cancer relies on the PDGFRβ–fibronectin axis for tumorsphere formation and metastatic spread

High-grade serous ovarian cancer (HGSOC) is the deadliest gynecological malignancy. The most common form of metastatic spread of HGSOC is transcoelomic dissemination. In this process, detached cells from the primary tumor aggregate as tumorspheres and promote the accumulation of peritoneal ascites....

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Detalhes bibliográficos
Autores: Gendrau-Sanclemente, Núria, Figueras, Agnès, Gracova, Kristina, Lahiguera, Álvaro, Alsina-Sanchís, Elisenda, Marín-Jiménez, Juan A., Vidal, August, Matias-Guiu, Xavier, Fernandez-Gonzalez, Sergi, Barahona, Marc, Martí, Lola, Ponce, Jordi, Viñals, Francesc
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2024
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10459.1/467652
Acesso em linha:https://doi.org/10.1002/1878-0261
https://hdl.handle.net/10459.1/467652
Access Level:Acceso aberto
Palavra-chave:Fibronectin
HGSOC
Metastasis
Ovarian cancer
PDGFRβ
Tumorspheres
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repository_id_str
spelling Ovarian cancer relies on the PDGFRβ–fibronectin axis for tumorsphere formation and metastatic spreadGendrau-Sanclemente, NúriaFigueras, AgnèsGracova, KristinaLahiguera, ÁlvaroAlsina-Sanchís, ElisendaMarín-Jiménez, Juan A.Vidal, AugustMatias-Guiu, XavierFernandez-Gonzalez, SergiBarahona, MarcMartí, LolaPonce, JordiViñals, FrancescFibronectinHGSOCMetastasisOvarian cancerPDGFRβTumorspheresHigh-grade serous ovarian cancer (HGSOC) is the deadliest gynecological malignancy. The most common form of metastatic spread of HGSOC is transcoelomic dissemination. In this process, detached cells from the primary tumor aggregate as tumorspheres and promote the accumulation of peritoneal ascites. This represents an early event in HGSOC development and is indicative of poor prognosis. In this study, based on tumorspheres isolated from ascitic liquid samples from HGSOC patients, ovarian cancer spheroid 3D cultures, and in vivo models, we describe a key signal for tumorsphere formation in HGSOC. We report that platelet-derived growth factor receptor beta (PDGFRβ) is essential for fibronectin-mediated cell clustering of ovarian cancer cells into tumorspheres. This effect is mediated by the kinase NUAK family SNF1-like kinase 1 (NUAK1) and blocked by PDGFRβ pharmacological or genetic inhibition. In the absence of PDGFRβ, ovarian cancer cells can be provided with fibronectin by cancer-associated fibroblasts to generate chimeric spheroids. This work provides new insights that uncover potential targets to prevent peritoneal dissemination, the main cause of advanced disease in HGSOC patients.John Wiley & Sons Ltd2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.1002/1878-0261https://hdl.handle.net/10459.1/467652reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1002/1878-0261Molecular Oncology, 2024, vol. 18, núm.1, p. 136-155, 2024cc-by (c)The Authors, 2023Attribution 4.0 Internationalinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/oai:recercat.cat:10459.1/4676522026-05-29T05:05:01Z
dc.title.none.fl_str_mv Ovarian cancer relies on the PDGFRβ–fibronectin axis for tumorsphere formation and metastatic spread
title Ovarian cancer relies on the PDGFRβ–fibronectin axis for tumorsphere formation and metastatic spread
spellingShingle Ovarian cancer relies on the PDGFRβ–fibronectin axis for tumorsphere formation and metastatic spread
Gendrau-Sanclemente, Núria
Fibronectin
HGSOC
Metastasis
Ovarian cancer
PDGFRβ
Tumorspheres
title_short Ovarian cancer relies on the PDGFRβ–fibronectin axis for tumorsphere formation and metastatic spread
title_full Ovarian cancer relies on the PDGFRβ–fibronectin axis for tumorsphere formation and metastatic spread
title_fullStr Ovarian cancer relies on the PDGFRβ–fibronectin axis for tumorsphere formation and metastatic spread
title_full_unstemmed Ovarian cancer relies on the PDGFRβ–fibronectin axis for tumorsphere formation and metastatic spread
title_sort Ovarian cancer relies on the PDGFRβ–fibronectin axis for tumorsphere formation and metastatic spread
dc.creator.none.fl_str_mv Gendrau-Sanclemente, Núria
Figueras, Agnès
Gracova, Kristina
Lahiguera, Álvaro
Alsina-Sanchís, Elisenda
Marín-Jiménez, Juan A.
Vidal, August
Matias-Guiu, Xavier
Fernandez-Gonzalez, Sergi
Barahona, Marc
Martí, Lola
Ponce, Jordi
Viñals, Francesc
author Gendrau-Sanclemente, Núria
author_facet Gendrau-Sanclemente, Núria
Figueras, Agnès
Gracova, Kristina
Lahiguera, Álvaro
Alsina-Sanchís, Elisenda
Marín-Jiménez, Juan A.
Vidal, August
Matias-Guiu, Xavier
Fernandez-Gonzalez, Sergi
Barahona, Marc
Martí, Lola
Ponce, Jordi
Viñals, Francesc
author_role author
author2 Figueras, Agnès
Gracova, Kristina
Lahiguera, Álvaro
Alsina-Sanchís, Elisenda
Marín-Jiménez, Juan A.
Vidal, August
Matias-Guiu, Xavier
Fernandez-Gonzalez, Sergi
Barahona, Marc
Martí, Lola
Ponce, Jordi
Viñals, Francesc
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Fibronectin
HGSOC
Metastasis
Ovarian cancer
PDGFRβ
Tumorspheres
topic Fibronectin
HGSOC
Metastasis
Ovarian cancer
PDGFRβ
Tumorspheres
description High-grade serous ovarian cancer (HGSOC) is the deadliest gynecological malignancy. The most common form of metastatic spread of HGSOC is transcoelomic dissemination. In this process, detached cells from the primary tumor aggregate as tumorspheres and promote the accumulation of peritoneal ascites. This represents an early event in HGSOC development and is indicative of poor prognosis. In this study, based on tumorspheres isolated from ascitic liquid samples from HGSOC patients, ovarian cancer spheroid 3D cultures, and in vivo models, we describe a key signal for tumorsphere formation in HGSOC. We report that platelet-derived growth factor receptor beta (PDGFRβ) is essential for fibronectin-mediated cell clustering of ovarian cancer cells into tumorspheres. This effect is mediated by the kinase NUAK family SNF1-like kinase 1 (NUAK1) and blocked by PDGFRβ pharmacological or genetic inhibition. In the absence of PDGFRβ, ovarian cancer cells can be provided with fibronectin by cancer-associated fibroblasts to generate chimeric spheroids. This work provides new insights that uncover potential targets to prevent peritoneal dissemination, the main cause of advanced disease in HGSOC patients.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1002/1878-0261
https://hdl.handle.net/10459.1/467652
url https://doi.org/10.1002/1878-0261
https://hdl.handle.net/10459.1/467652
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1002/1878-0261
Molecular Oncology, 2024, vol. 18, núm.1, p. 136-155, 2024
dc.rights.none.fl_str_mv cc-by (c)The Authors, 2023
Attribution 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
rights_invalid_str_mv cc-by (c)The Authors, 2023
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv John Wiley & Sons Ltd
publisher.none.fl_str_mv John Wiley & Sons Ltd
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869419533274447873
score 15,811543

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