Exosomes from differentially activated macrophages influence dormancy or resurgence of breast cancer cells within bone marrow stroma

Walker, Nykia D.; Elias, Michael; Guiro, Khadidiatou; Bhatia, Ranvir; Greco, Steven J.; Bryan, Margarette; Gergues, Marina; Sandiford, Oleta A.; Ponzio, Nicholas M.; Leibovich, Samuel; Rameshwar, Pranela

doi:10.1038/s41419-019-1304-z

Cited by 85 publications

(93 citation statements)

References 49 publications

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“…Exosomes recently obtained from both types of these multi-functional macrophages [174], isolated from M2a and M2b, presented strong anti-inflammatory activity, through the Th2 activation and immunoregulation [175]. In addition, M2a-exosomes are capable of regulating the behaviour of breast cancer cells by inducing or reversing their dormancy [176].…”

Section: Exosomes Derived From Immune System-related Cells That Play mentioning

confidence: 99%

Exosome: A New Player in Translational Nanomedicine

Aheget

Tristán‐Manzano

Mazini

et al. 2020

JCM

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Summary: Exosomes are extracellular vesicles released by the vast majority of cell types both in vivo and ex vivo, upon the fusion of multivesicular bodies (MVBs) with the cellular plasma membrane. Two main functions have been attributed to exosomes: their capacity to transport proteins, lipids and nucleic acids between cells and organs, as well as their potential to act as natural intercellular communicators in normal biological processes and in pathologies. From a clinical perspective, the majority of applications use exosomes as biomarkers of disease. A new approach uses exosomes as biologically active carriers to provide a platform for the enhanced delivery of cargo in vivo. One of the major limitations in developing exosome-based therapies is the difficulty of producing sufficient amounts of safe and efficient exosomes. The identification of potential proteins involved in exosome biogenesis is expected to directly cause a deliberate increase in exosome production. In this review, we summarize the current state of knowledge regarding exosomes, with particular emphasis on their structural features, biosynthesis pathways, production techniques and potential clinical applications.

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Section: Exosomes Derived From Immune System-related Cells That Play mentioning

confidence: 99%

Exosome: A New Player in Translational Nanomedicine

Aheget

Tristán‐Manzano

Mazini

et al. 2020

JCM

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“…Стволовые клетки немезенхимального происхождения выделяли из жировой ткани [8,35,37], использовали ство ловые клетки-предшественники нервной ткани [4,38], резидуальные стволовые клетки печени [16,20], а так же индуцированные плюрипотентные стволовые клетки (iPS cells) [48]. Иные клеточные источники: предшественники кардиомиоцитов [2,3,49], макрофаги [12,14,15,50,51], T-лимфоциты [44] и гранулоциты [43]. В ряде случаев ВВ получали не из клеточных культур, а из биологических жидкостей, например, семенной жидкости [52] и плазмы крови [14,52].…”

Section: путь введения эффектunclassified

“…Пролиферативный эффект наблюдался у кератиноцитов HaCat через стимуляцию AKT и ERK сиг- [2,6,7,9,11,49] Увеличение выживаемости [2,6,7,9,11,50] микроРНК-21 [49], микроРНК-125b-5p [6], микроРНК-486-5p [11] Сигнальный путь Akt/Sfrp2 [9] Кардиомиоциты HL-1 [3] Подавление апоптоза [3] микроРНК-132, микроРНК-210, микроРНК-146a-3p, микроРНК-181 [3] Кардиомиоциты мыши [8] Подавление апоптоза [8] микроРНК-214 [8] Эндотелиоциты пупочной вены человека HUVEC [2-4, 9, 18, 37, 40] Увеличение пролиферативной активности [2,4,9,37,40] Индукция ангиогенеза [2,3,9,18,37] Увеличение миграции [4,9,37,40] микроРНК-132 [3], микроРНК-126 [18] VEGF [37,40], PDGFA, EGF, FGF2 [37] Сигнальные пути PI3K/AKT и MAPK/ERK1/2 [40] Сигнальный путь AKT, ERK [37] Эндотелиоциты лёгочной артерии PAEC [28] Антиапоптотический эффект Увеличение ангиогенеза Увеличение миграции…”

Section: таблица 1 продолжениеunclassified

“…Другие исследователи пришли к выводу, что доставка к клеткам глиомы через гематоэнцефалический барьер улучшалась, а период циркуляции препарата, заключённого в везикулы, увеличивался [14]. Везикулы М1-макрофагов увеличивают чувствительность опухолевых клеток рака молочной железы к химиопрепаратам путём активации NFκB-пути, а М2-макрофагов -оставляют клетки в покоящемся состоянии, не давая им пролиферировать [50].…”

Section: In Vivo исследованияunclassified

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Extracellular vesicles therapy: opportunities, mechanisms and perspectives

Великонивцев¹,

Головкин²

2020

Russ J Cardiol

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Extracellular vesicles are biological membrane-coated objects with size less then 1000 nm. They can contain variety of biologically active molecules (such as proteins, miRNA, mRNA, DNA etc.) and also are able to provide intercellular communications and implement lots if biological functions. Now possibilities of using extracellular vesicles for therapeutic approaches against various diseases and pathological conditions are rapidly discovered. In the most of cases mesenchymal stem cells are the sources of extracellular vesicles and miRNAs which vesicles transport are considered to be causable agents of their activities. In-vitro studies show that extracellular vesicles provide anti-inflammatory, anti-apoptotic activities and can stimulate angiogenesis and regeneration. Performed studies which were analyzed and structurized by us in this review demonstrate current perspectives for clinical use of extracellular vesicles in the therapy of such clinical conditions as oxidative stress, ischemia-reperfusion injury, tumor growth etc.

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“…Consistently, both clinical and experimental evidence demonstrate the importance of tumor microenvironment in breast cancer invasiveness. Two of the most abundant immune cell populations found in the stroma of breast cancer are tumorassociated macrophages (TAMs) representing up to 50% of the tumor mass and T cells (10)(11)(12)(13)(14). Both of them might have been associated with a poor prognosis and detrimental clinical outcome in breast cancer patients, likely by promoting the epithelial to mesenchymal transition (EMT) process, metastasis, and angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Identification and Validation of Stage-Associated PBMC Biomarkers in Breast Cancer Using MS-Based Proteomics

et al. 2020

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Background: It is well-described that the transcriptome of peripheral blood mononuclear cells (PBMCs) can be altered in the context of many malignancies to allow them avoid the effective immune response, which leads to cancer invasiveness. Here, we used an MS-based strategy to discover biomarkers in the PBMCs of breast cancer (BC) patients and validated them at different stages of BC. Methods: PBMCs were isolated from the breast cancer patients and were cultured alone or co-cultured with breast cancer cell lines. The role of PBMC in the invasion property of breast cancer cells was explored. NF-kB activity was also measured in the co-cultured breast cancer cells. Identification of protein profiles in the secretome and proteome of the co-cultured PBMCs was performed using SWATH mass spectrometry. Pathway enrichment and gene ontology analyses were carried out to look for the molecular pathways correlated with the protein expression profile of PBMCs in the breast cancer patients. Quantitative real-time polymerase chain reaction (qPCR) was performed to validate the candidate genes in the PBMC fraction of the breast cancer patients at the primary and metastatic stages. In silico survival analysis was performed to assess the potential clinical biomarkers in these PBMC subtypes. Results: PBMCs could significantly increase the invasion property of the BC cells concomitant with a decrease in E-cadherin and an increase in both Vimentin and N-cadherin expression. The NF-kB activity in the BC cells significantly increased following co-culturing implying the role of PBMCs in EMT induction. Enrichment analysis showed that the differentially expressed proteins in PBMCs are mainly associated with IL-17, PI3K-Akt, and HIF-1 signaling pathway, in which a set of seven proteins including TMSB4X, HSPA4, S100A9, SRSF6, THBS1, CUL4A, and CANX were frequently expressed. Finally, in silico analysis confirmed that a gene set consisting of S100A9, SRSF6, THBS1, CUL4A, and CANX were found to provide an insight for the identification of metastasis in breast cancer patients. Moradpoor et al. Stage-Associated PBMC Biomarkers, BCs Conclusion: In conclusion, our study revealed that the protein expression profile in PBMCs is a reflection of the proteins expressed in the BC tissue itself; however, the abundance level is different due to the stage of cancer.

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Exosomes from differentially activated macrophages influence dormancy or resurgence of breast cancer cells within bone marrow stroma

Cited by 85 publications

References 49 publications

Exosome: A New Player in Translational Nanomedicine

Exosome: A New Player in Translational Nanomedicine

Extracellular vesicles therapy: opportunities, mechanisms and perspectives

Identification and Validation of Stage-Associated PBMC Biomarkers in Breast Cancer Using MS-Based Proteomics

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