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.

Small extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix / 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. - In: MOLECULAR ONCOLOGY. - ISSN 1574-7891. - ELETTRONICO. - 15:(2021), pp. 3596-3614. [10.1002/1878-0261.13110]

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

Ridolfi, Andrea;
2021

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.
2021
15
3596
3614
Goal 3: Good health and well-being for people
Bortot, Barbara; Apollonio, Maura; Rampazzo, Enrico; Valle, Francesco; Brucale, Marco; Ridolfi, Andrea; Ura, Blendi; Addobbati, Riccardo; Di Lorenzo, ...espandi
File in questo prodotto:
File Dimensione Formato  
Molecular Oncology - 2021 - Bortot - Small extracellular vesicles from malignant ascites of patients with advanced ovarian.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Creative commons
Dimensione 2.26 MB
Formato Adobe PDF
2.26 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1245690
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 16
  • ???jsp.display-item.citation.isi??? 16
social impact