Plasma exosomes stimulate breast cancer metastasis through surface interactions and activation of FAK signaling

Shtam, Tatiana; Naryzhny, Stanislav N.; Samsonov, Roman; Karasik, David; Mizgirev, I. V.; Kopylov, Arthur T.; Petrenko, Elena; Zabrodskaya, Yana A.; Kamyshinsky, Roman; Nikitin, Daniil; Sorokin, Maxim; Buzdin, Anton; Gil-Henn, Hava; Malek, Anastasia

doi:10.1007/s10549-018-5043-0

Cited by 41 publications

(40 citation statements)

References 50 publications

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“…The detected size of the vesicles and their concentration evaluated using NTA was in accordance with previous data [7,23]. It should be noted that the obtained concentration of CSF vesicles is two orders of magnitude lower than that described for peripheral blood plasma [22,24].…”

Section: Discussionsupporting

confidence: 91%

“…Taking into account the obtained data on the concentration of vesicles in CSF, as well as our own experience in visualization of EVs from different biofluids by cryo-EM [20][21][22] we pooled all particle samples (from about 30 mL of CSF for PD patients and 50 mL for the comparison group) for re-ultracentrifugation to maximize the number of EVs in the final pellet. NTA of the sample of vesicles isolated from pooled CSF of PD patients showed that the particles generally varied in size from 26 to 305 nm and that the vesicular size mode, D90 and concentration were 69 nm, 125 nm and 0.6x10 12 particles/ml, respectively ( Fig 1B).…”

Section: Characterization Of Evs By Nta and Flow Cytometry Analysismentioning

confidence: 99%

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Cryo-electron microscopy of extracellular vesicles from cerebrospinal fluid

et al. 2020

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Extracellular vesicles (EVs) are membrane-enclosed vesicles which play important role for cell communication and physiology. EVs are found in many human biological fluids, including blood, breast milk, urine, cerebrospinal fluid (CSF), ejaculate, saliva etc. These nanosized vesicles contain proteins, mRNAs, microRNAs, non-coding RNAs and lipids that are derived from producing cells. EVs deliver complex sets of biological information to recipient cells thereby modulating their behaviors by their molecular cargo. In this way EVs are involved in the pathological development and progression of many human disorders, including neurodegenerative diseases. In this study EVs purified by ultracentrifugation from CSF of patients with Parkinson's disease (PD) and individuals of the comparison group were characterized using nanoparticle tracking analysis, flow cytometry and cryo-electron microscopy. Vesicular size and the presence of exosomal marker CD9 on the surface provided evidence that most of the EVs were exosome-like vesicles. Cryo-electron microscopy allowed us to visualize a large spectrum of extracellular vesicles of various size and morphology with lipid bilayers and vesicular internal structures. Thus, we described the diversity and new characteristics of the vesicles from CSF suggesting that subpopulations of EVs with different and specific functions may exist.

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Section: Discussionsupporting

confidence: 91%

Section: Characterization Of Evs By Nta and Flow Cytometry Analysismentioning

confidence: 99%

Cryo-electron microscopy of extracellular vesicles from cerebrospinal fluid

et al. 2020

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“…The importance of exosomes in governing various physiological and pathological conditions is no longer in doubt. Exosomes may transfer signals to induce EMT, cell migration and invasion, angiogenesis, and metastasis processes [ 5 , 8 , 9 , 10 , 11 ]. It should be noted that the majority of studies were performed with exosomes from cell culture.…”

Section: Discussionmentioning

confidence: 99%

“…For example, plasma exosomes of different origins affect circulating tumor cells and exosomes secreted by stromal cells affect tumor cells. Indeed, it was shown that exosomes from healthy donors’ plasma have potency in stimulating the metastasis-promoting properties of breast cancer cells [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

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

Konoshenko

Sagaradze

Orlova

et al. 2020

IJMS

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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.

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Recent advancements in the study of breast cancer exosomes as mediators of intratumoral communication

Groza

Zimța

Irimie

et al. 2019

Journal Cellular Physiology

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Breast cancer is a heterogeneous disease, with a morbidity rate of 27.8% and a mortality rate of 15% among women population worldwide. Understanding how this cancer develops and the mechanisms behind tumor progression and chemoresistance is of utmost importance. Exosomes mediate communication in a population of heterogeneous tumoral cells. They have a cargo composed of oncogenes and oncomiRs which change the transcriptomic scenario of their targeted cells and activate numerous tumor-promoting signaling pathways. Exosomes secreted by breast cancer cells lead to enhanced cell proliferation, replicative immortality, angiogenesis, invasion, migration, and chemoresistance. Studying exosomes from this perspective offers more in depth understanding of breast malignancy and may aid in the future development of early diagnostic, prognostic and therapeutic options. We present the latest findings in this area and offer practical solutions which may further stimulate the much-needed research of exosome in breast cancer.

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Plasma exosomes stimulate breast cancer metastasis through surface interactions and activation of FAK signaling

Cited by 41 publications

References 50 publications

Cryo-electron microscopy of extracellular vesicles from cerebrospinal fluid

Cryo-electron microscopy of extracellular vesicles from cerebrospinal fluid

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

Recent advancements in the study of breast cancer exosomes as mediators of intratumoral communication

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