In women, breast cancer (BC) is the most commonly diagnosed cancer (24.5%) and the leading cause of cancer death (15.5%). Understanding how this heterogeneous disease develops and the confirm mechanisms behind tumor progression is of utmost importance. Exosomes are long-range message vesicles that mediate communication between cells in physiological conditions but also in pathology, such as breast cancer. In recent years, there has been an exponential rise in the scientific studies reporting the change in morphology and cargo of tumor-derived exosomes. Due to the transfer of biologically active molecules, such as RNA (microRNA, long non-coding RNA, mRNA, etc.) and proteins (transcription factors, enzymes, etc.) into recipient cells, these lipid bilayer 30–150 nm vesicles activate numerous signaling pathways that promote tumor development. In this review, we attempt to shed light on exosomes’ involvement in breast cancer pathogenesis (including epithelial-to-mesenchymal transition (EMT), tumor cell proliferation and motility, metastatic processes, angiogenesis stimulation, and immune system repression). Moreover, the potential use of exosomes as promising diagnostic biomarkers for liquid biopsy of breast cancer is also discussed.
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.
Introduction. Ovarian cancer (OC) is one of the malignant neoplasms of the female reproductive system with a high mortality rate. Currently used tumor markers of this pathology do not have high sensitivity and specificity. In this regard, promising areas of molecular oncology are the study of the mechanisms of carcinogenesis of OC and the search for new biomarkers of liquid biopsy for early non-invasive diagnosis of neoplasms. It is known that tumor cells actively secrete exosomes into the extracellular space, which include biologically active molecules involved in carcinogenesis and claiming to be diagnostic markers. It was previously shown that microRNA-24 (miR-24) and microRNA-101 (miR-101) are transported as part of exosomes in OC and are involved in the degradation of the extracellular matrix, stromal remodeling, angiogenesis, and cancer cell motility.Aim. To evaluate the representation and diagnostic significance of miR-24 and miR-101 in plasma exosomes and ascitic fluid of OC patients.Materials and methods. The study included blood and ascitic fluid samples from OC patients (n = 20) and blood samples from healthy women (n = 19). The exosomal nature of the vesicles was confirmed by transmission electron microscopy, nanotracing analysis, and flow cytometry. After isolation of exosomal RNA, the relative level of miRNA was determined using reverse transcription and real-time polymerase chain reaction.Results. The highest concentration of exosomes was found in the ascitic fluid of OC patients, while the concentration of exosomes in the blood plasma of these patients was significantly higher than in healthy women. Relative levels of miR-24 and miR-101 in exosomes of blood plasma of healthy women were significantly higher than in exosomes of blood plasma and ascitic fluid of OC patients; at the same time, the levels of these miRNAs in exosomes of plasma and ascitic fluid of patients did not differ significantly.Conclusion. The results obtained confirm the promise of exosomal miR-101 and miR-24 for the diagnosis of OC by liquid biopsy.
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