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....
| Autores: | ; ; ; ; ; ; ; ; ; ; ; ; |
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| Tipo de documento: | Artigo |
| Estado: | Published version |
| Data de publicação: | 2023 |
| País: | España |
| Recursos: | Universidad de Barcelona |
| Repositório: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/221876 |
| Acesso em linha: | https://hdl.handle.net/2445/221876 |
| Nível de acesso: | Acesso aberto |
| Palavra-chave: | Ascites Càncer d'ovari Fibroblasts Ovarian cancer |
| _version_ | 1878738952445231104 |
|---|---|
| author | Gendrau-Sanclemente, Núria |
| 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 |
| author_browse | Alsina Sanchís, Elisenda Barahona, Marc Fernández González, Sergi Figueras i Amat, Agnès Gendrau-Sanclemente, Núria Gracova, Kristina Lahiguera, Álvaro Martí, Lola Marín Jiménez, Juan A. Matias-Guiu, Xavier, 1958- Ponce i Sebastià, Jordi Vidal-Bel, August Viñals Canals, Francesc |
| 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 |
| collection | Dipòsit Digital de la UB |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_b84051cdffd57b60f2216f287c46d4bd |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/221876 |
| publishDate | 2023 |
| publishDateSort | 2023 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| reponame_str | Dipòsit Digital de la UB |
| spelling | Ovarian cancer relies on the PDGFRβ-fibronectin axis for tumorsphere formation and metastatic spread 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 Ascites Càncer d'ovari Fibroblasts Ovarian cancer 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. Elsevier https://hdl.handle.net/2445/221876 |
| spellingShingle | Ovarian cancer relies on the PDGFRβ-fibronectin axis for tumorsphere formation and metastatic spread Gendrau-Sanclemente, Núria Ascites Càncer d'ovari Fibroblasts Ovarian cancer |
| status_str | publishedVersion |
| title | 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_short | 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 |
| topic | Ascites Càncer d'ovari Fibroblasts Ovarian cancer |
| topic_facet | Ascites Càncer d'ovari Fibroblasts Ovarian cancer |
| url | https://hdl.handle.net/2445/221876 |