Small extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix. Issue 12 (27th October 2021)

• Record Type: Journal Article
• Authors: Bortot, Barbara; Apollonio, Maura; Rampazzo, Enrico; Valle, Francesco; Brucale, Marco; Ridolfi, Andrea; Ura, Blendi; Addobbati, Riccardo; Di Lorenzo, Giovanni; Romano, Federico; Buonomo, Francesca; Ripepi, Chiara; Ricci, Giuseppe; Biffi, Stefania
• Is Part Of: Molecular oncology. Volume 15:Issue 12(2021)
• Page Start: 3596
• Page End: 3614
• Publication Date: 2021-10-27
• Subjects: ascites -- chemotherapy -- extracellular matrix -- extracellular vesicles -- fibronectin -- ovarian cancer; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.13110
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : 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. Abstract : The mechanisms by which extracellular vesicles (EVs) promote ovarian cancer progression in the pre‐metastatic niche have not been fully discovered. This study showed that sampling ascites before and after chemotherapy allows characterizing small‐EVs released by tumor cells, reflecting their biological status. Small‐EVs derived from ascitic fluid‐derived tumor cell cultures contained a robust proteomic profile of extracellular matrix remodeling regulators.