Ovarian-Cancer-Associated Extracellular Vesicles: Microenvironmental Regulation and Potential Clinical Applications

Abstract

Ovarian cancer (OC) is one of the most diagnosed gynecological cancers in women. Due to the lack of effective early stage screening, women are more often diagnosed at an advanced stage; therefore, it is associated with poor patient outcomes. There are a lack of tools to identify patients at the highest risk of developing this cancer. Moreover, early detection strategies, therapeutic approaches, and real-time monitoring of responses to treatment to improve survival and quality of life are also inadequate. Tumor development and progression are dependent upon cell-to-cell communication, allowing cancer cells to re-program cells not only within the surrounding tumor microenvironment, but also at distant sites. Recent studies established that extracellular vesicles (EVs) mediate bi-directional communication between normal and cancerous cells. EVs are highly stable membrane vesicles that are released from a wide range of cells, including healthy and cancer cells. They contain tissue-specific signaling molecules (e.g., proteins and miRNA) and, once released, regulate target cell phenotypes, inducing a pro-tumorigenic and immunosuppressive phenotype to contribute to tumor growth and metastasis as well as proximal and distal cell function. Thus, EVs are a “fingerprint” of their cell of origin and reflect the metabolic status. Additionally, via the capacity to evade the immune system and remain stable over long periods in circulation, EVs can be potent therapeutic agents. This review examines the potential role of EVs in the different aspects of the tumor microenvironment in OC, as well as their application in diagnosis, delivery of therapeutic agents, and disease monitoring.

Protein Panel of Serum-Derived Small Extracellular Vesicles for the Screening and Diagnosis of Epithelial Ovarian Cancer

“…In ovarian cancer, protein and miRNA are the main objects of sEV components considered as biomarkers for diagnosis and/or prognosis and are closely correlated to drug resistance, tumor microenvironment, and immune regulation [ 27 ]. We established a three-protein model for liquid biopsy for ovarian cancer with minimal loss of diagnostic efficacy, which showed good diagnostic efficacy even in the early-stage disease.…”

Plasma Exosomes of Patients with Breast and Ovarian Tumors Contain an Inactive 20S Proteasome

“…Although malignant cells themselves are the major source of tumorigenesis, their interactions with the tumor microenvironment are critical for the progression from a single tumor mass to distant metastases [26]. It was shown that exosomes carry messages (proteins, non-coding RNA, DNA, lipids, metabolites) from transformed healthy cells or to other cells in the tumor or they may signal in an autocrine manner back to the producing tumor cells causing changes in the recipient cells behavior and microenvironment alterations [27][28][29][30][31]. Moreover, cargo of exosomes from tumor microenvironments such as ascites fluids has been found to be highly immunosuppressive [32][33][34], helping cancer progression and metastasis.…”

New Approaches and Biomarker Candidates for the Early Detection of Ovarian Cancer

“…It is now well established that the proteomic profile of EXs can act as a useful tool or biomarker for diagnosing various types of cancer ( Nuzhat et al, 2017 ; Sharma et al, 2017 ; Kok and Yu, 2020 ; Croft et al, 2021 ). For example, a study by Klein-Scory et al (2014) illustrated that EXs secreted from pancreatic cancer cells had a distinctive proteomic profile allowing for possible use as an early stage biomarker ( Klein-Scory et al, 2014 ).…”