scholarly journals The basic characteristics of extracellular vesicles and their potential application in bone sarcomas

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shenglong Li
Keyword(s):  
Extracellular Vesicles ◽  
Membrane Vesicles ◽  
Bone Sarcoma ◽  
Biologically Active ◽  
Signal Molecules ◽  
Diagnosis And Prognosis ◽  
Bone Sarcomas ◽  
Basic Characteristics ◽  
Almost All ◽  
Sarcoma Cells

AbstractBone sarcomas are rare cancers accompanied by metastatic disease, mainly including osteosarcoma, Ewing sarcoma and chondrosarcoma. Extracellular vesicles (EVs) are membrane vesicles released by cells in the extracellular matrix, which carry important signal molecules, can stably and widely present in various body fluids, such as plasma, saliva and scalp fluid, spinal cord, breast milk, and urine liquid. EVs can transport almost all types of biologically active molecules (DNA, mRNA, microRNA (miRNA), proteins, metabolites, and even pharmacological compounds). In this review, we summarized the basic biological characteristics of EVs and focused on their application in bone sarcomas. EVs can be use as biomarker vehicles for diagnosis and prognosis in bone sarcomas. The role of EVs in bone sarcoma has been analyzed point-by-point. In the microenvironment of bone sarcoma, bone sarcoma cells, mesenchymal stem cells, immune cells, fibroblasts, osteoclasts, osteoblasts, and endothelial cells coexist and interact with each other. EVs play an important role in the communication between cells. Based on multiple functions in bone sarcoma, this review provides new ideas for the discovery of new therapeutic targets and new diagnostic analysis.

scholarly journals Extracellular Vesicles in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Functions and Applications

2021 ◽  
Vol 11 ◽  
Author(s):  
Bo Zhang ◽  
Ming Zhao ◽  
Qianjin Lu
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Autoimmune Diseases ◽  
Clinical Research ◽  
Extracellular Vesicles ◽  
Lupus Erythematosus ◽  
Membrane Vesicles ◽  
Systemic Lupus ◽  
Almost All ◽  
Extracellular Environment

In the last two decades, extracellular vesicles (EVs) have aroused wide interest among researchers in basic and clinical research. EVs, small membrane vesicles are released by almost all kinds of cells into the extracellular environment. According to many recent studies, EVs participate in immunomodulation and play an important role in the pathogenesis of autoimmune diseases. In addition, EVs have great potential in the diagnosis and therapy of autoimmune diseases. Here, we reviewed the latest research advances on the functions and mechanisms of EVs and their roles in the pathogenesis, diagnosis, and treatment of rheumatoid arthritis and systemic lupus erythematosus.

scholarly journals Extracellular vesicles in lung health, disease, and therapy

2019 ◽  
Vol 316 (6) ◽  
pp. L977-L989 ◽  
Author(s):  
Mark J. McVey ◽  
Mazharul Maishan ◽  
Kaj E. C. Blokland ◽  
Nathan Bartlett ◽  
Wolfgang M. Kuebler
Keyword(s):  
Lung Disease ◽  
Extracellular Vesicles ◽  
Biological Fluids ◽  
Biologically Active ◽  
Target Cells ◽  
Molecular Physiology ◽  
Diagnosis And Prognosis ◽  
Lung Physiology ◽  
Subcellular Membrane ◽  
Lung Health

Both physiological homeostasis and pathological disease processes in the lung typically result from complex, yet coordinated multicellular responses that are synchronized via paracrine and endocrine intercellular communication pathways. Of late, extracellular vesicles have emerged as important information shuttles that can coordinate and disseminate homeostatic and disease signals. In parallel, extracellular vesicles in biological fluids such as sputum, mucus, epithelial lining fluid, edema fluid, the pulmonary circulation, pleural fluid, and lymphatics have emerged as promising candidate biomarkers for diagnosis and prognosis in lung disease. Extracellular vesicles are small, subcellular, membrane-bound vesicles containing cargos from parent cells such as lipids, proteins, genetic information, or entire organelles. These cargos endow extracellular vesicles with biologically active information or functions by which they can reprogram their respective target cells. Recent studies show that extracellular vesicles found in lung-associated biological fluids play key roles as biomarkers and effectors of disease. Conversely, administration of naïve or engineered extracellular vesicles with homeostatic or reparative effects may provide a promising novel protective and regenerative strategy to treat lung disease. To highlight this rapidly developing field, the American Journal of Physiology-Lung Cellular and Molecular Physiology is now launching a special Call for Papers on extracellular vesicles in lung health, disease, and therapy. This review aims to set the stage for this call by introducing extracellular vesicles and their emerging roles in lung physiology and pathobiology.

scholarly journals Leucine and branched-chain amino acid metabolism contribute to the growth of bone sarcomas by regulating AMPK and mTORC1 signaling

2020 ◽  
Vol 477 (9) ◽  
pp. 1579-1599 ◽  
Author(s):  
Shailer B. Martin ◽  
William S. Reiche ◽  
Nicholas A. Fifelski ◽  
Alexander J. Schultz ◽  
Spencer J. Stanford ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Differential Expression ◽  
Mammalian Target Of Rapamycin ◽  
Carbon Sources ◽  
Bone Sarcoma ◽  
Structural Analog ◽  
Mtorc1 Signaling ◽  
Bone Sarcomas ◽  
Branched Chain ◽  
Sarcoma Cells

Osteosarcoma and chondrosarcoma are sarcomas of the bone and the cartilage that are primarily treated by surgical intervention combined with high toxicity chemotherapy. In search of alternative metabolic approaches to address the challenges in treating bone sarcomas, we assessed the growth dependence of these cancers on leucine, one of the branched-chain amino acids (BCAAs), and BCAA metabolism. Tumor biopsies from bone sarcoma patients revealed differential expression of BCAA metabolic enzymes. The cytosolic branched-chain aminotransferase (BCATc) that is commonly overexpressed in cancer cells, was down-regulated in chondrosarcoma (SW1353) in contrast with osteosarcoma (143B) cells that expressed both BCATc and its mitochondrial isoform BCATm. Treating SW1353 cells with gabapentin, a selective inhibitor of BCATc, further revealed that these cells failed to respond to gabapentin. Application of the structural analog of leucine, N-acetyl-leucine amide (NALA) to disrupt leucine uptake, indicated that all bone sarcoma cells used leucine to support their energy metabolism and biosynthetic demands. This was evident from the increased activity of the energy sensor AMP-activated protein kinase (AMPK), down-regulation of complex 1 of the mammalian target of rapamycin (mTORC1), and reduced cell viability in response to NALA. The observed changes were most profound in the 143B cells, which appeared highly dependent on cytosolic and mitochondrial BCAA metabolism. This study thus demonstrates that bone sarcomas rely on leucine and BCAA metabolism for energy and growth; however, the differential expression of BCAA enzymes and the presence of other carbon sources may dictate how efficiently these cancer cells take advantage of BCAA metabolism.

scholarly journals Extracellular vesicles as biomarkers and therapeutic targets for cancer

2020 ◽  
Vol 318 (1) ◽  
pp. C29-C39 ◽  
Author(s):  
Fumihiko Urabe ◽  
Nobuyoshi Kosaka ◽  
Kagenori Ito ◽  
Takahiro Kimura ◽  
Shin Egawa ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Lipid Membrane ◽  
Therapeutic Targets ◽  
Membrane Vesicles ◽  
Clinical Applications ◽  
Research Knowledge ◽  
Cellular Processes ◽  
Novel Strategy ◽  
Almost All

Extracellular vesicles (EVs) are small lipid membrane vesicles that are secreted from almost all kinds of cells into the extracellular space. EVs are widely accepted to be involved in various cellular processes; in particular, EVs derived from cancer cells have been reported to play important roles in modifying the tumor microenvironment and promoting tumor progression. In addition, EVs derived from cancer cells encapsulate various kinds of tumor-specific molecules, such as proteins and RNAs, which contribute to cancer malignancy. Therefore, the unveiling of the precise mechanism of intercellular communication via EVs in cancer patients will provide a novel strategy for cancer treatment. Furthermore, a focus on the contents of EVs could promote the use of EVs in body fluids as clinically useful diagnostic and prognostic biomarkers. In this review, we summarize the current research knowledge on EVs as biomarkers and therapeutic targets and discuss their potential clinical applications.

P2583Endothelial cell-derived extracellular vesicles promote M2 polarization of THP-1 cells

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Fruehwald ◽  
A Zietzer ◽  
G Nickenig ◽  
N Werner ◽  
F Jansen
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Extracellular Vesicles ◽  
Biologically Active ◽  
Signal Molecules ◽  
M2 Macrophage ◽  
Macrophage Phenotype ◽  
Protective Function ◽  
Vascular Regeneration ◽  
Tnf Α

Abstract Introduction The intercellular transfer of biologically active molecules in extracellular vesicles (EVs) has recently been discovered as an important mechanism, which regulates cardiovascular health and disease. In the context of atherosclerosis, endothelial cell-derived EVs have been shown to modulate the phenotype of EV recipient cells in a relevant manner. Under pro-atherogenic conditions e.g. hyperglycemia, the export of numerous signal molecules in EVs is altered and so are EV-dependent effects on recipient cells. While the effect of endothelial-cell derived EVs on other endothelial cells and vascular smooth muscle cells is well characterized, little is known about the vesicle-based interaction of endothelial cells and monocytes under pro-atherogenic conditions. This is particularly relevant as monocytes are crucial modulators of vascular regeneration and inflammation. Our aim was therefore to investigate, whether EVs from endothelial cells have a significant effect on the differentiation and polarization of monocytes and how this process is affected by pathologic conditions as mentioned above. Methods and results Human Coronary Arterial Endothelial Cells (HCAECs) were cultured in high-Glucose-medium (30 mM) for 72h. PBS was used as a control. Large EVs were isolated from the culture supernatant by differential centrifugation (1 x 1500 g / 15 min + 2 x 2ehz748.0909 g / 40 min). The harvested large EVs were characterized by Immunoblotting, Nanoparticle Tracking Analysis as well as Transmission electron microscopy and were shown to be mostly between 80 and 500 nm in size. Specific surface markers including Annexin V and Flotillin-1 were highly enriched in the isolated EVs. The EVs were used for co-culture with THP-1 cells with and without previous phorbol-12-myristate-13-acetate (PMA) stimulation. After 4h as well as after 24 h of incubation with EVS, total RNA was isolated from the THP-1 cells and qPCR was performed to assess polarization towards M1 by TNF-α gene expression or M2 by IL-10 expression. While EV treatment of THP-1 cells without previous PMA-stimulation showed no measurable effect, a significant decrease in the expression of TNF-α was detected after 4 h of treatment from Glucose injured HCAECs. Similar results were obtained without glucose stimulation, the most significant reduction of TNF-α expression however was seen at 24 h. In regard to IL-10 no significant expression changes were detected in EV treated THP-1 cells. Conclusion We showed that glucose injury does not relevantly affect vesicle release or size. Furthermore, endothelial cell derived EVs cause a reduction of TNF-α expression, which indicates a polarization towards an M2 macrophage phenotype, irrespective of prior hyperglycaemic injury. As the M2 phenotype has been described as pro-regenerative, we conclude that endothelial cell derived EVs can exert a protective function during the invasion of monocytes in cardiovascular disease and remodeling.

scholarly journals Emerging roles of extracellular vesicles in physiology and disease

2020 ◽  
Author(s):  
Rikinari Hanayama
Keyword(s):  
Communication Networks ◽  
Extracellular Vesicles ◽  
Culture Media ◽  
Membrane Vesicles ◽  
Cell Types ◽  
Target Cells ◽  
Cell Culture Media ◽  
Research Fields ◽  
Research Findings ◽  
Almost All

Abstract Extracellular vesicles (EVs), such as exosomes and microvesicles, are small membrane vesicles secreted by almost all cell types and are abundant in blood, body fluids, such as urine, spinal fluid, tears and saliva, and cell culture media. From an evolutionary perspective, they are biologically significant as a means for expelling unwanted cellular contents. Recently, EVs have received considerable attention as messengers of intercellular communication networks, allowing the exchange of proteins and lipids between the cells producing them and target cells that trigger various cellular responses. EVs also carry mRNAs and microRNAs inside them, transferring genetic information among cells. In addition, the expression pattern of these molecules is related to the cellular state and the progression of diseases, and the search for biomarkers within the EV is underway in many research fields. However, the physiological and pathophysiological roles of EVs remain largely elusive. Therefore, in this special issue, we have compiled reviews of the latest research findings on EV research.

scholarly journals Role for extracellular vesicles in the tumour microenvironment

2017 ◽  
Vol 373 (1737) ◽  
pp. 20160488 ◽  
Author(s):  
Ana O'Loghlen
Keyword(s):  
Cardiovascular Diseases ◽  
Nucleic Acids ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Intercellular Communication ◽  
Membrane Vesicles ◽  
Tumour Microenvironment ◽  
Cellular Behaviour ◽  
Almost All ◽  
Behaviour Changes

Extracellular vesicles (EVs) are small-membrane vesicles secreted by most cells types with the role to provide intercellular communication both locally and systemically. The transfer of their content between cells, which includes nucleic acids, proteins and lipids, confers the means for these interactions and induces significant cellular behaviour changes in the receiving cell. EVs are implicated in the regulation of numerous physiological and pathological processes, including development and neurological and cardiovascular diseases. Importantly, it has been shown that EV signalling is essential in almost all the steps necessary for the progress of carcinomas, from primary tumours to metastasis. In this review, we will focus on the latest findings for EV biology in relation to cancer progression and the tumour microenvironment. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.

The size of extracellular vesicles secreted by different types of stem cells

2018 ◽  
pp. 38-42
Author(s):  
И.Б. Алчинова ◽  
М.В. Полякова ◽  
И.Н. Сабурина ◽  
М.Ю. Карганов
Keyword(s):  
Stem Cells ◽  
Extracellular Vesicles ◽  
Culture Media ◽  
Living Organism ◽  
Isolation And Characterization ◽  
Transmission Electron ◽  
Study Results ◽  
Multipotent Mesenchymal Stem Cells ◽  
Rat Adipose Tissue ◽  
Almost All

Механизм терапевтического действия мультипотентных мезенхимных стволовых клеток (ММСК) на облученный организм в последнее время вызывает повышенный интерес исследователей. В качестве активного участника паракринного механизма реализации этого эффекта предлагают рассматривать внеклеточные везикулы, секретируемые практически всеми клетками живого организма. Цель работы: выделить и охарактеризовать внеклеточные везикулы, продуцируемые стволовыми клетками различной природы. Материалы и методы. Суспензии внеклеточных везикул, выделенных по модифицированному протоколу дифференциального центрифугирования из культуральных жидкостей от культур ММСК костного мозга человека 2-го пассажа и ММСК жировой ткани крысы 4-го пассажа, были проанализированы методом просвечивающей электронной микроскопии и методом анализа траекторий наночастиц. Результаты. Исследование показало наличие в обоих образцах микрочастиц размерами до и около 100 нм, однако процентное содержание частиц разных размеров в суспензии различалось для двух анализируемых типов клеток. Заключение. Полученные результаты могут свидетельствовать о специфике секреции, обусловленной клеточным типом. A mechanism of the therapeutic effect of multipotent mesenchymal stem cells (MMSC) on irradiated body has recently arisen much interest of researchers. Extracellular vesicles (EVs) secreted by almost all cells of a living organism were suggested to actively contribute to the paracrine mechanism of this effect. The aim of the study was isolation and characterization of extracellular vesicles produced by various types of stem cells. Materials and methods. Suspensions of EVs were isolated from culture media of passage 2 human bone marrow-derived MMSC and passage 4 rat adipose tissue-derived MMSC using a modified protocol of differential centrifugation and then studied using transmission electron microscopy and nanoparticle tracking analysis. Results. The study showed the presence of microparticles with a size of >100 nm in the examined samples. However, the percent content of particles with different sizes in the suspension was different in two analyzed types of cell culture. Conclusion. The study results might reflect a specificity of secretion determined by the cell type.

scholarly journals Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development

2021 ◽  
Vol 22 (9) ◽  
pp. 4823
Author(s):  
María Fernanda González ◽  
Paula Díaz ◽  
Alejandra Sandoval-Bórquez ◽  
Daniela Herrera ◽  
Andrew F. G. Quest
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Extracellular Vesicles ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Gastric Epithelium ◽  
Infected Cells ◽  
H Pylori

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

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