ABSTRACT
Ovarian cancer (OC) has the highest mortality rate among all gynecologic cancers and is characterized by early peritoneal spread. The growth and development of OC are associated with the formation of ascitic fluid, creating a unique tumor microenvironment. Understanding the mechanisms of tumor progression is crucial in identifying new diagnostic biomarkers and developing novel therapeutic strategies. Exosomes, lipid bilayer vesicles measuring 30-150 nm in size, are known to establish a crucial link between malignant cells and their microenvironment. Additionally, the confirmed involvement of exosomes in carcinogenesis enables them to mediate the invasion, migration, metastasis, and angiogenesis of tumor cells. Functionally active non-coding RNAs (such as microRNAs, long non-coding RNAs, circRNAs), proteins, and lipid rafts transported within exosomes can activate numerous signaling pathways and modify gene expression. This review aims to expand our understanding of the role of exosomes and their contents in OC carcinogenesis processes such as epithelial-mesenchymal transition (EMT), angiogenesis, vasculogenic mimicry, tumor cell proliferation, and peritoneal spread. It also discusses the potential for utilizing exosomal cargo to develop novel "liquid biopsy" biomarkers for early OC diagnosis.
ABSTRACT
Ovarian cancer (OC) is one of the most common and fatal types of gynecological cancer. In the early phase of OC detection, the current treatment and diagnostic methods are not efficient and sensitive enough. Therefore, it is crucial to explore the mechanisms of OC metastasis and discover valuable factors for early diagnosis of female cancers and novel therapeutic strategies for metastasis. Exosomes are known to be involved in the development, migration, and invasion of cancer cells, and their cargo could be useful for the non-invasive biopsy development. CD151- and Tspan8-positive exosomes are known to support the degradation of the extracellular matrix, and are involved in stroma remodeling, angiogenesis and cell motility, as well as the association of miR-24 and miR-101 with these processes. The objective of this study was to explore the relationship of these components of exosomal cargo, in patients with OC, to clarify the clinical significance of these markers in liquid biopsies. The levels of tetraspanins Tspan8+ and CD151+ exosomes were significantly higher in plasma exosomes of OC patients compared with healthy females (HFs). The relative levels of miR-24 and miR-101 in plasma exosomes of HFs were significantly higher than in plasma exosomes of OC patients, while the levels of these microRNAs in exosomes from plasma and ascites of ill females showed no difference. Our study revealed a strong direct correlation between the change in the ascites exosomes CD151+Tspan8+ subpopulation level and the expression levels of the ascites (R = 0.81, p < 0.05) and plasma exosomal miR-24 (R = 0.74, p < 0.05) in OC patients, which confirms the assumption that exosomal cargo act synergistically to increase cellular motility, affecting cellular processes and signaling. Bioinformatics analysis confirmed the involvement of CD151 and Tspan8 tetraspanins and genes controlled by miR-24-3p and miR-101 in signaling pathways, which are crucial for carcinogenesis, demonstrating that these tetraspanins and microRNAs are potential biomarkers for OC screening, and predictors of poor clinicopathological behavior in tumors.