Abstract
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.
Highlights
Exosomes are small endosome-derived vesicles (30–120 nm) that are secreted by multiple cell types into the extracellular space [1]
We have found that single exosomes predominate in the plasma of healthy female donors (HFs) and in the plasma and total blood of breast cancer patients (BCPs), while their proportion in the total blood of HFs is reduced by almost 2.5 times
We found that the proportion of blood cell-associated exosomes isolated from blood of BCPs is decreased if compared to HFs [17,35]
Summary
Exosomes are small endosome-derived vesicles (30–120 nm) that are secreted by multiple cell types into the extracellular space [1] The size of these vesicles allows them to penetrate from various tissues into blood and back, interacting with target cells or tissues. Exosomes carry multiple receptors and ligands on their surface that are responsible for the biodistribution and binding of vesicles to target cells [2,3] This allows the exosomes to transfer different types of RNA and functionally active proteins, providing cell-to-cell communication [4,5]. Increasing attention is paid to the pathological role of exosomes produced by cancer cells in tumorigenesis These vesicles are able to carry molecular messages from transformed to healthy cells or to other cells in the tumor, or they may signal in an autocrine manner, causing changes in the recipient cell’s behavior and microenvironment alterations [6]. The detection, isolation. and profiling of cancer-specific exosomes from blood plasma is still challenging, since the share of such vesicles does not exceed 1–2% [15,16]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
