Document Type: Research Articles
Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia.
Novosibirsk State University, Novosibirsk, Russia.
Cancer Research Institute, Тomsk National Research Medical Center, Russian Academy of Science, Tomsk, Russia, Tomsk, Russia.
Siberian State Medical University, Tomsk, Russia.
Regional Clinical Oncological Hospital, Novosibirsk, Russia.
Novosibirsk Research Institute of Circulation Pathology Academician E.N. Meshalkin, Novosibirsk, Russia.
Background: 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.