Total blood exosomes in breast cancer: Potential role in crucial steps of tumorigenesis

Maria Konoshenko, Georgy Sagaradze, Evgeniya Orlova, Tatiana Shtam, Ksenia Proskura, Roman Kamyshinsky, Natalia Yunusova, Antonina Alexandrova, Anastasia Efimenko, Svetlana Tamkovich

Результат исследования: Научные публикации в периодических изданияхстатьярецензирование

Аннотация

Exosomes are crucial players in cell-to-cell communication and are involved in tumorigenesis. There are two fractions of blood circulating exosomes: free and cell-surface-associated. Here, we compared the effect of total blood exosomes (contain plasma exosomes and blood cell-surface-associated exosomes) and plasma exosomes from breast cancer patients (BCPs, n = 43) and healthy females (HFs, n = 35) on crucial steps of tumor progression. Exosomes were isolated by ultrafiltration, followed by ultracentrifugation, and characterized by cryo-electron microscopy (cryo-EM), nanoparticle tracking analysis, and flow cytometry. Cryo-EM revealed a wider spectrum of exosome morphology with lipid bilayers and vesicular internal structures in the HF total blood in comparison with plasma. No differences in the morphology of both exosomes fractions were detected in BCP blood. The plasma exosomes and total blood exosomes of BCPs had different expression levels of tumor-associated miR-92a and miR-25-3p, induced angiogenesis and epithelial-to-mesenchymal transition (EMT), and increased the number of migrating pseudo-normal breast cells and the total migration path length of cancer cells. The multidirectional effects of HF total blood exosomes on tumor dissemination were revealed; they suppress the angiogenesis and total migration path length of MCF10A, but stimulate EMT and increase the number of migrating MCF10A and the total path length of SKBR3 cells. In addition, HF plasma exosomes enhance the metastasis-promoting properties of SKBR3 cells and stimulate angiogenesis. Both cell-free and blood cell-surface-associated exosomes are involved in the crucial stages of carcinogenesis: the initiation of EMT and the stimulation of proliferation, cell migration, and angiogenesis. Thus, for the estimation of the diagnostic/prognostic significance of circulating exosomes in the blood of cancer patients more correctly, the total blood exosomes, which consist of plasma exosomes and blood cell-surface-associated exosomes should be used.

Язык оригиналаанглийский
Номер статьи7341
Страницы (с-по)1-18
Число страниц18
ЖурналInternational Journal of Molecular Sciences
Том21
Номер выпуска19
DOI
СостояниеОпубликовано - 1 окт 2020

Fingerprint Подробные сведения о темах исследования «Total blood exosomes in breast cancer: Potential role in crucial steps of tumorigenesis». Вместе они формируют уникальный семантический отпечаток (fingerprint).

Цитировать