Small extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix

The exact role of malignant ascites in the development of intraperitoneal metastases remains unclear, and the mechanisms by which extracellular vesicles (EVs) promote tumor progression in the pre‐metastatic niche have not been fully discovered. In this study, we characterized ascites from high‐grade...

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Autores principales:	Barbara Bortot, Maura Apollonio, Enrico Rampazzo, Francesco Valle, Marco Brucale, Andrea Ridolfi, Blendi Ura, Riccardo Addobbati, Giovanni Di Lorenzo, Federico Romano, Francesca Buonomo, Chiara Ripepi, Giuseppe Ricci, Stefania Biffi
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	ascites chemotherapy extracellular matrix extracellular vesicles fibronectin ovarian cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/06acab89ee58474dbda22c51f9a15593
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spelling	oai:doaj.org-article:06acab89ee58474dbda22c51f9a155932021-12-02T10:31:06ZSmall extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix1878-02611574-789110.1002/1878-0261.13110https://doaj.org/article/06acab89ee58474dbda22c51f9a155932021-12-01T00:00:00Zhttps://doi.org/10.1002/1878-0261.13110https://doaj.org/toc/1574-7891https://doaj.org/toc/1878-0261The exact role of malignant ascites in the development of intraperitoneal metastases remains unclear, and the mechanisms by which extracellular vesicles (EVs) promote tumor progression in the pre‐metastatic niche have not been fully discovered. In this study, we characterized ascites from high‐grade epithelial ovarian cancer patients. Small‐EVs (30–150 nm) were isolated from two sources—the bulk ascites and the ascitic fluid‐derived tumor cell cultures—and assessed with a combination of imaging, proteomic profiling, and protein expression analyses. In addition, Gene Ontology and pathway analysis were performed using different databases and bioinformatic tools. The results proved that the small‐EVs derived from the two sources exhibited significantly different stiffness and size distributions. The bulk ascitic fluid‐derived small‐EVs were predominantly involved in the complement and coagulation cascade. Small‐EVs derived from ascites cell cultures contained a robust proteomic profile of extracellular matrix remodeling regulators, and we observed an increase in transforming growth factor‐β‐I (TGFβI), plasminogen activator inhibitor 1 (PAI‐1), and fibronectin expression after neoadjuvant chemotherapy. When measured in the two sources, we demonstrated that fibronectin exhibited opposite expression patterns in small‐EVs in response to chemotherapy. These findings highlight the importance of an ascites cell isolation workflow in investigating the treatment‐induced cancer adaption processes.Barbara BortotMaura ApollonioEnrico RampazzoFrancesco ValleMarco BrucaleAndrea RidolfiBlendi UraRiccardo AddobbatiGiovanni Di LorenzoFederico RomanoFrancesca BuonomoChiara RipepiGiuseppe RicciStefania BiffiWileyarticleasciteschemotherapyextracellular matrixextracellular vesiclesfibronectinovarian cancerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Oncology, Vol 15, Iss 12, Pp 3596-3614 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ascites chemotherapy extracellular matrix extracellular vesicles fibronectin ovarian cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	ascites chemotherapy extracellular matrix extracellular vesicles fibronectin ovarian cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Barbara Bortot Maura Apollonio Enrico Rampazzo Francesco Valle Marco Brucale Andrea Ridolfi Blendi Ura Riccardo Addobbati Giovanni Di Lorenzo Federico Romano Francesca Buonomo Chiara Ripepi Giuseppe Ricci Stefania Biffi Small extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix
description	The exact role of malignant ascites in the development of intraperitoneal metastases remains unclear, and the mechanisms by which extracellular vesicles (EVs) promote tumor progression in the pre‐metastatic niche have not been fully discovered. In this study, we characterized ascites from high‐grade epithelial ovarian cancer patients. Small‐EVs (30–150 nm) were isolated from two sources—the bulk ascites and the ascitic fluid‐derived tumor cell cultures—and assessed with a combination of imaging, proteomic profiling, and protein expression analyses. In addition, Gene Ontology and pathway analysis were performed using different databases and bioinformatic tools. The results proved that the small‐EVs derived from the two sources exhibited significantly different stiffness and size distributions. The bulk ascitic fluid‐derived small‐EVs were predominantly involved in the complement and coagulation cascade. Small‐EVs derived from ascites cell cultures contained a robust proteomic profile of extracellular matrix remodeling regulators, and we observed an increase in transforming growth factor‐β‐I (TGFβI), plasminogen activator inhibitor 1 (PAI‐1), and fibronectin expression after neoadjuvant chemotherapy. When measured in the two sources, we demonstrated that fibronectin exhibited opposite expression patterns in small‐EVs in response to chemotherapy. These findings highlight the importance of an ascites cell isolation workflow in investigating the treatment‐induced cancer adaption processes.
format	article
author	Barbara Bortot Maura Apollonio Enrico Rampazzo Francesco Valle Marco Brucale Andrea Ridolfi Blendi Ura Riccardo Addobbati Giovanni Di Lorenzo Federico Romano Francesca Buonomo Chiara Ripepi Giuseppe Ricci Stefania Biffi
author_facet	Barbara Bortot Maura Apollonio Enrico Rampazzo Francesco Valle Marco Brucale Andrea Ridolfi Blendi Ura Riccardo Addobbati Giovanni Di Lorenzo Federico Romano Francesca Buonomo Chiara Ripepi Giuseppe Ricci Stefania Biffi
author_sort	Barbara Bortot
title	Small extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix
title_short	Small extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix
title_full	Small extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix
title_fullStr	Small extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix
title_full_unstemmed	Small extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix
title_sort	small extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/06acab89ee58474dbda22c51f9a15593
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Small extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix

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