Breast cancer and ovarian cancer are the most common types of tumor worldwide among women. Despite the active distribution of mammography, the proportion of primary-identified breast cancer patients (BCPs) at an advanced stage of the disease remains high (Witten and Parker, 2018). Most ovarian cancer patients (OCPs) are diagnosed at an advanced stage also and 70% of patients present with lymph node metastasis and ascites fluids (Dong et al., 2014). Cancer patients with metastasis have a higher rate of treatment failure and mortality (Ferlay et al., AbstractBackground: As is known, exosomes play an important role in promoting progression of cancers by increasing its invasive potential. The aim of this study was to evaluate the levels of tetraspanine-associated (ADAM-10) and tetraspanine-nonassociated proteases (20S proteasomes) in exosomes from culture medium, plasma exosomes of patients with breast tumors and plasma and ascites of ovarian tumor patients. Methods: MCF-7 and SVO-3 culture mediums and blood samples from healthy females (n = 30, HFs), patients with diffuse dyshormonal dysplasia of the breast (n=28, BBTPs), breast cancer patients (n=32, BCPs), borderline ovarian tumor patients (n=20, BOTPs) and blood and ascites samples ovarian cancer patients (n=35, OCPs) were included in the study. Exosomes from plasma, ascites and culture mediums were isolated and characterized in according to Extracellular Vesicles Society. The expression levels of 20S proteasome and ADAM-10 in exosomes were determined using flow cytometry and western blot analysis, correspondingly. Results: The subpopulation composition of the exosomes from MCF-7 culture medium and from blood plasma of HFs and breast diseases patients is similar, however CD9/CD24 subpopulation significantly increased at cell supernatant. The similar results was obtained for exosomes from SVO-3 medium and blood plasma and ascites of ovary tumor patients, but CD9/CD24 subpopulation significantly decreased at cells and illness samples, however CD63/CD24 exosomes increased significantly from cell supernatant. 20S proteasome level is significantly increased in exosomes from MCF-7 and SVO-3 culture medium, breast tumor patients and OCPs plasma in comparison to HUVEC culture medium and HFs plasma samples. At CD9-positive exosomes from BCPs plasma and MCF-7 was reveal a high expression of ADAM-10 and low expression is from BBDPs plasma and ovarian tumor patients plasma/ ascites samples. Exosomes from ascites OCP had high expression of ADAM-10 in the CD24-positive subpopulation. Conclusion: Breast and ovarian cancer development is connected with functioning of immune proteasome forms in plasma and ascites exosomes, while increased ADAM10 expression at CD9-positive exosome was associated with breast cancer and at CD24-positive subpopulation -with ovarian cancer. Obtained data confirm role of exosomal proteases in tumor progression.

A simple approach for isolation of exosomes from the blood plasma, which allows to obtain highly purified preparations of microvesicles no larger than 100 nm has been proposed. The presence of different subpopulations of exosomes in the blood plasma of healthy donors and cancer patients has been recognized. We found the presence of the universal markers CD9, CD24 and CD81 on exosomes isolated from blood plasma that can be used to their routine typing.

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It is known that exosomes are involved in the cancer development, including by increasing the motility of tumor cells and increasing their invasive potential. Since it is not clear how involved the exosomes associated with the blood cell surface are in the dissemination of the tumor process, this paper is devoted to assessing the level of tetraspanin-associated metal-loproteinase ADAM-10 on the surface of plasma exosomes and total exosomes of blood of clinically healthy women (n = 30), patients with mastopathy (n = 28) and breast cancer (n = 32). Microvesicles from blood samples and culture medium MCF-7 were isolated by ultrafiltration and ultracentrifugation. Using flow cytofluorimetry with antibodies against universal exosomal markers, it was found that CD9 and CD24-positive exosome subpopulations predominate in preparations of microvesicles from the blood of healthy women and tumor patients. A comparative analysis of the ADAM-10 level on the surface of plasma exosomes and total exosomes in the blood of healthy women and tumor patients showed the absence of significant differences in both microvesicle subpopulations, except for patients with luminal type breast cancer. In the latter case, on the surface of CD9-positive plasma exosomes, a significant increase in sheddase level and a decrease were found on the surface of total exosomes, correlating with an increase in the proportion of freely circulating exosomes in plasma. The obtained data suggest that an increase in the ADAM-10 level on the exosome surface at breast cancer development reduces the possibility of vesicle attached to blood cells, thus increasing their concentration in the blood, which in turn allows exosomes to act as mediators in ensuring intercellular communication, influencing the development of both primary tumors and distant metastases. In addition, an increased level of ADAM-10 on the surface of exosomes of breast cancer patients can largely determine tumor growth and dissemination, modifying the local microenvironment and making growth factors contained in the matrix available on the one hand and, dissolving the components of the extracellular matrix and increasing migration and invasive activity of tumor cells on the other.

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