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....
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2024 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10459.1/467652 |
| Online Access: | https://doi.org/10.1002/1878-0261 https://hdl.handle.net/10459.1/467652 |
| Access Level: | Open access |
| Keyword: | Fibronectin HGSOC Metastasis Ovarian cancer PDGFRβ Tumorspheres |
| _version_ | 1878739953595187201 |
|---|---|
| author | Gendrau-Sanclemente, Núria |
| 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 |
| author_browse | Alsina-Sanchís, Elisenda Barahona, Marc Fernandez-Gonzalez, Sergi Figueras, Agnès Gendrau-Sanclemente, Núria Gracova, Kristina Lahiguera, Álvaro Martí, Lola Marín-Jiménez, Juan A. Matias-Guiu, Xavier Ponce, Jordi Vidal, August Viñals, Francesc |
| 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 |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| 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_cb0fd6ade03b028b7cdab5c3e976f8ce |
| institution | 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) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:10459.1/467652 |
| publishDate | 2024 |
| publishDateSort | 2024 |
| publisher | John Wiley & Sons Ltd |
| publisherStr | John Wiley & Sons Ltd |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | Ovarian cancer relies on the PDGFRβ–fibronectin axis for tumorsphere formation and metastatic spread 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 Fibronectin HGSOC Metastasis Ovarian cancer PDGFRβ Tumorspheres 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. John Wiley & Sons Ltd https://doi.org/10.1002/1878-0261 https://hdl.handle.net/10459.1/467652 |
| 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 |
| 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 | Fibronectin HGSOC Metastasis Ovarian cancer PDGFRβ Tumorspheres |
| topic_facet | Fibronectin HGSOC Metastasis Ovarian cancer PDGFRβ Tumorspheres |
| url | https://doi.org/10.1002/1878-0261 https://hdl.handle.net/10459.1/467652 |