Total Blood Exosomes in Breast Cancer: Potential Role in Crucial Steps of Tumorigenesis

被引：27

作者：

Konoshenko, Maria ^{[1
]}

Sagaradze, Georgy ^{[2
]}

Orlova, Evgeniya ^{[3
]}

Shtam, Tatiana ^{[4
,5
]}

Proskura, Ksenia ^{[1
,6
]}

Kamyshinsky, Roman ^{[5
,7
,8
]}

Yunusova, Natalia ^{[9
,10
]}

Alexandrova, Antonina ^{[3
]}

Efimenko, Anastasia ^{[2
]}

Tamkovich, Svetlana ^{[1
,11
]}

机构：

[1] Russian Acad Sci, Inst Chem Biol & Fundamental Med, Siberian Branch, Novosibirsk 630090, Russia

[2] Lomonosov Moscow State Univ, Med Res & Educ Ctr, Moscow 119991, Russia

[3] Minist Hlth Russian Federat, NN Blokhin Canc Res Ctr, Moscow 115478, Russia

[4] Kurchatov Inst, BP Konstantinov Natl Res Ctr, Petersburg Nucl Phys Inst, Gatchina 188300, Russia

[5] Kurchatov Inst, Natl Res Ctr, Moscow 123182, Russia

[6] Novosibirsk Reg Clin Oncol Dispensary, Novosibirsk 630108, Russia

[7] Moscow Inst Phys & Technol, Dolgoprudnyi 141700, Moscow Region, Russia

[8] Russian Acad Sci, Shubnikov Inst Crystallog, Fed Sci Res Ctr Crystallog & Photon, Moscow 119333, Russia

[9] Russian Acad Sci, Canc Res Inst, Tomsk Natl Res Med Ctr, Tomsk 634050, Russia

[10] Siberian State Med Univ, Fac Med & Biol, Dept Biochem & Mol Biol, Tomsk 634050, Russia

[11] Novosibirsk State Univ, Dept Mol Biol & Biotechnol, Fac Nat Sci, Novosibirsk 630090, Russia

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 19期

基金：

俄罗斯科学基金会;

关键词：

exosomes; migration; angiogenesis; cryo-electron microscopy; microRNAs; breast cancer; EXTRACELLULAR VESICLES; CIRCULATING EXOSOMES;

D O I：

10.3390/ijms21197341

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1 / 18

页数：18

共 48 条

[1] Tumor Cell Malignant Properties Are Enhanced by Circulating Exosomes in Sleep Apnea [J].