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  • Title: Small extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix.
    Author: Bortot B, Apollonio M, Rampazzo E, Valle F, Brucale M, Ridolfi A, Ura B, Addobbati R, Di Lorenzo G, Romano F, Buonomo F, Ripepi C, Ricci G, Biffi S.
    Journal: Mol Oncol; 2021 Dec; 15(12):3596-3614. PubMed ID: 34614287.
    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.
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