Malignant-ascites-derived small extracellular vesicles in advanced ovarian cancer patients: insights into the dynamics of the extracellular matrix


Posted: 2021-10-06 19:00:00
. 2021 Oct 6. doi: 10.1002/1878-0261.13110. Online ahead of print. Barbara Bortot 1 , Maura Apollonio 2 , Enrico Rampazzo 3 , Francesco Valle 4 5 , Marco Brucale 4 5 , Andrea Ridolfi 4 6 , Blendi Ura 7 , Riccardo Addobbati 8 , Giovanni Di Lorenzo 7 , Federico Romano 7 , Francesca Buonomo 7 , Chiara Ripepi 7 , Giuseppe Ricci 7 9 , Stefania Biffi 7 Affiliations Expand Affiliations 1 Department of Medical Genetics, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy. 2 Pediatric Department, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy. 3 Department of Chemistry "Giacomo Ciamician", University of Bologna, Bologna, Italy. 4 Consorzio Sistemi a Grande Interfase, Department of Chemistry, University of Firenze, Firenze, Italy. 5 Consiglio Nazionale delle Ricerche, Istituto per lo Studio dei Materiali Nanostrutturati (CNRISMN), Bologna, Italy. 6 Department of Chemistry, University of Firenze, Firenze, Italy. 7 Obstetrics and Gynecology, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy. 8 Department of Clinical Toxicology, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy. 9 Clinical Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy. Item in Clipboard Barbara Bortot et al. Mol Oncol. 2021. Show details Display options Display options Format . 2021 Oct 6. doi: 10.1002/1878-0261.13110. Online ahead of print. Authors Barbara Bortot 1 , Maura Apollonio 2 , Enrico Rampazzo 3 , Francesco Valle 4 5 , Marco Brucale 4 5 , Andrea Ridolfi 4 6 , Blendi Ura 7 , Riccardo Addobbati 8 , Giovanni Di Lorenzo 7 , Federico Romano 7 , Francesca Buonomo 7 , Chiara Ripepi 7 , Giuseppe Ricci 7 9 , Stefania Biffi 7 Affiliations 1 Department of Medical Genetics, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy. 2 Pediatric Department, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy. 3 Department of Chemistry "Giacomo Ciamician", University of Bologna, Bologna, Italy. 4 Consorzio Sistemi a Grande Interfase, Department of Chemistry, University of Firenze, Firenze, Italy. 5 Consiglio Nazionale delle Ricerche, Istituto per lo Studio dei Materiali Nanostrutturati (CNRISMN), Bologna, Italy. 6 Department of Chemistry, University of Firenze, Firenze, Italy. 7 Obstetrics and Gynecology, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy. 8 Department of Clinical Toxicology, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy. 9 Clinical Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy. Item in Clipboard CiteDisplay options Display options Format 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 pathways 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 distribution. 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 cells isolation workflow in investigating the treatment-induced cancer adaption processes. Keywords: ascites; chemotherapy; extracellular matrix (ECM); extracellular vesicles; fibronectin; ovarian cancer. This article is protected by copyright. All rights reserved. [x] Cite Copy Format: Send To [x]

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