Protease Cargo in Circulating Exosomes of Breast Cancer and Ovarian Cancer Patients

乳腺癌和卵巢癌患者循环外泌体中的蛋白酶货物

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作者:Svetlana N Tamkovich, Natalia V Yunusova, Elena Tugutova, Anton K Somov, Ksenia V Proskura, Larisa A Kolomiets, Marina N Stakheeva, Alina E Grigor’eva, Pavel P Laktionov, Irina V Kondakova

Background

As is known, exosomes play an important role in promoting progression of cancers by increasing its invasive potential. The

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.

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.

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