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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Autores: Gendrau-Sanclemente, Núria, Figueras i Amat, Agnès, Gracova, Kristina, Lahiguera, Álvaro, Alsina Sanchís, Elisenda, Marín Jiménez, Juan A., Vidal-Bel, August, Matias-Guiu, Xavier, 1958-, Fernández González, Sergi, Barahona, Marc, Martí, Lola, Ponce i Sebastià, Jordi, Viñals Canals, Francesc
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/221876
Acceso en línea:https://hdl.handle.net/2445/221876
Access Level:acceso abierto
Palabra clave:Ascites
Càncer d'ovari
Fibroblasts
Ovarian cancer
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spelling Ovarian cancer relies on the PDGFRβ-fibronectin axis for tumorsphere formation and metastatic spreadGendrau-Sanclemente, NúriaFigueras i Amat, AgnèsGracova, KristinaLahiguera, ÁlvaroAlsina Sanchís, ElisendaMarín Jiménez, Juan A.Vidal-Bel, AugustMatias-Guiu, Xavier, 1958-Fernández González, SergiBarahona, MarcMartí, LolaPonce i Sebastià, JordiViñals Canals, FrancescAscitesCàncer d'ovariFibroblastsAscitesOvarian cancerFibroblastsHigh-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.Elsevier2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/221876Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1002/1878-0261.13556Molecular Oncology, 2023, vol. 18, num.1, p. 136-155https://doi.org/10.1002/1878-0261.13556cc-by (c) Gendrau-Sanclemente, N. et al., 2023http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2218762026-05-27T06:46:51Z
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
Ascites
Càncer d'ovari
Fibroblasts
Ascites
Ovarian cancer
Fibroblasts
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 i Amat, Agnès
Gracova, Kristina
Lahiguera, Álvaro
Alsina Sanchís, Elisenda
Marín Jiménez, Juan A.
Vidal-Bel, August
Matias-Guiu, Xavier, 1958-
Fernández González, Sergi
Barahona, Marc
Martí, Lola
Ponce i Sebastià, Jordi
Viñals Canals, Francesc
author Gendrau-Sanclemente, Núria
author_facet Gendrau-Sanclemente, Núria
Figueras i Amat, Agnès
Gracova, Kristina
Lahiguera, Álvaro
Alsina Sanchís, Elisenda
Marín Jiménez, Juan A.
Vidal-Bel, August
Matias-Guiu, Xavier, 1958-
Fernández González, Sergi
Barahona, Marc
Martí, Lola
Ponce i Sebastià, Jordi
Viñals Canals, Francesc
author_role author
author2 Figueras i Amat, Agnès
Gracova, Kristina
Lahiguera, Álvaro
Alsina Sanchís, Elisenda
Marín Jiménez, Juan A.
Vidal-Bel, August
Matias-Guiu, Xavier, 1958-
Fernández González, Sergi
Barahona, Marc
Martí, Lola
Ponce i Sebastià, Jordi
Viñals Canals, Francesc
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ascites
Càncer d'ovari
Fibroblasts
Ascites
Ovarian cancer
Fibroblasts
topic Ascites
Càncer d'ovari
Fibroblasts
Ascites
Ovarian cancer
Fibroblasts
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 2023
dc.date.none.fl_str_mv 2023
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://hdl.handle.net/2445/221876
url https://hdl.handle.net/2445/221876
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/10.1002/1878-0261.13556
Molecular Oncology, 2023, vol. 18, num.1, p. 136-155
https://doi.org/10.1002/1878-0261.13556
dc.rights.none.fl_str_mv cc-by (c) Gendrau-Sanclemente, N. et al., 2023
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Gendrau-Sanclemente, N. et al., 2023
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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