Abstract
Extracellular vesicles (EVs) are a heterogeneous group of cell-derived submicron vesicles released under physiological or pathological conditions. EVs mediate the cellular crosstalk, thus contributing to defining the tumor microenvironment, including in epithelial ovarian cancer (EOC). The available literature investigating the role of EVs in EOC has been reviewed following PRISMA guidelines, focusing on the role of EVs in early disease diagnosis, metastatic spread, and the development of chemoresistance in EOC. Data were identified from searches of Medline, Current Contents, PubMed, and from references in relevant articles from 2010 to 1 April 2020. The research yielded 194 results. Of these, a total of 36 papers, 9 reviews, and 27 original types of research were retained and analyzed. The literature findings demonstrate that a panel of EV-derived circulating miRNAs may be useful for early diagnosis of EOC. Furthermore, it appears clear that EVs are involved in mediating two crucial processes for metastatic and chemoresistance development: the epithelial–mesenchymal transition, and tumor escape from the immune system response. Further studies, more focused on in vivo evidence, are urgently needed to clarify the role of EV assessment in the clinical management of EOC patients.
Highlights
Despite the efforts made in recent decades to improve the efficacy of therapeutic strategies, epithelial ovarian cancer (EOC) remains the most lethal among gynecological malignancies
This topic has been recently addressed in a literature review by Nakamura et al [6], in which several exosome-derived molecules were identified as involved in invasion, migration, and metastatic spread and identified as unfavorable prognostic biomarkers in malignant ascites, including: signal transducer and activator of transcription 3 (STAT3)/Fas; epithelial cell adhesion molecule (EpCAM); membrane-type 1, 2, and 9 MMP (MMP-1; MMP-2; MMP-9); urokinase-type plasminogen activator; and soluble L1 adhesion molecule (CD171)
Experimental achievements have clearly demonstrated that the microenvironment plays a crucial role in driving tumor development, and metastatic spread, in EOC
Summary
Despite the efforts made in recent decades to improve the efficacy of therapeutic strategies, epithelial ovarian cancer (EOC) remains the most lethal among gynecological malignancies. In approximately 70% of patients, EOC is diagnosed as late stage disease with a 5-year overall survival below 40% [4,5,6], emphasizing the need to develop highly sensitive, non-invasive tools able to ensure an early diagnosis, addressing one of the biggest challenges in biomarker research As previously highlighted, another crucial point in EOC research is certainly represented by the development of drug resistance [6,7,8]. In this context, growing attention has been focused on the role of extracellular vesicles (EVs) and their cargoes as prognostic and predictive factors in EOC patients These micro-environmental structures are involved in cellular crosstalk, contributing to several physiological responses, such as metabolism regulation and activation of stress response, but, at the same time, EVs may represent an effective tool for cancer tissue to maintain its own pathological homeostasis [6,7,8]. We review here the available literature investigating the role of EVs in OC patients, trying to emphasize the clinical implication in the diagnosis and treatment of this challenging malignancy
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