Circulating Extracellular Vesicles in Gynecological Tumors: Realities and Challenges

Abstract

Although liquid biopsy can be considered a reality for the clinical management of some cancers, such as lung or colorectal cancer, it remains a promising field in gynecological tumors. In particular, circulating extracellular vesicles (cEVs) secreted by tumor cells represent a scarcely explored type of liquid biopsy in gynecological tumors. Importantly, these vesicles are responsible for key steps in tumor development and dissemination and are recognized as major players in cell-to-cell communication between the tumor and the microenvironment. However, limited work has been reported about the biologic effects and clinical value of EVs in gynecological tumors. Therefore, here we review the promising but already relatively limited data on the role of circulating EVs in promoting gynecological tumor spread and also their value as non-invasive biomarkers to improve the management of these type of tumors.

Keywords: biomarkers; circulating extracellular vesicles (cEVs); endometrial cancer (EC); liquid biopsy; ovarian cancer (OC).

Figure 1

Extracellular vesicle (EV) biogenesis and secretion. EVs are classified into three major subtypes on the basis of biogenic and morphological properties: exosomes, microvesicles (MVs), and apoptotic bodies. Exosomes are nanostructures of approximately 30–100 nm in diameter that originate as intraluminal vesicles (ILV) in multivesicle endosomes (MVB), which are intermediates in the endosomal system and can fuse with the plasma membrane and secrete their contents in exosomes into the extracellular space. Microvesicles (50–2,000 nm) are generated by direct budding and fission of the plasma membrane into the extracellular space. Apoptotic bodies (500–4,000 nm) are released by the blebbing process during programmed cell death. EVs contain several cell-specific components, such as proteins, lipids, and nucleic acids (DNA, mRNA, miRNA, and lncRNA) that are transferred to target cells (10, 11).