Biology and biogenesis of shed microvesicles

Small GTPases, Journal Year: 2016, Volume and Issue: 8(4), P. 220 - 232

Published: Aug. 5, 2016

The ability of cells to transmit bioactive molecules recipient and the extracellular environment is a fundamental requirement for both normal physiology disease pathogenesis. It has traditionally been thought that soluble factors released from were responsible this cellular signaling but recent research revealed role microvesicles in process. Microvesicles are heterogeneous membrane-bound sacs shed surface into highly regulated They following selective incorporation host molecular cargo including multiple types proteins nucleic acids. In addition providing new insight etiology complex human diseases, also show great promise as tool advanced diagnosis therapy we move forward age personalized medicine. Here review current status rapidly evolving field microvesicle biology, highlighting critical regulatory roles several small GTPases biology biogenesis microvesicles.

Language: Английский

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The hypoxic tumor microenvironment: A driving force for breast cancer progression

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2015, Volume and Issue: 1863(3), P. 382 - 391

Published: June 14, 2015

Language: Английский

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Tumor microenvironment: Challenges and opportunities in targeting metastasis of triple negative breast cancer

Pharmacological Research, Journal Year: 2020, Volume and Issue: 153, P. 104683 - 104683

Published: Feb. 9, 2020

Language: Английский

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Extracellular membrane vesicles in the three domains of life and beyond

FEMS Microbiology Reviews, Journal Year: 2018, Volume and Issue: 43(3), P. 273 - 303

Published: Nov. 20, 2018

Cells from all three domains of life, Archaea, Bacteria and Eukarya, produce extracellular vesicles (EVs) which are sometimes associated with filamentous structures known as nanopods or nanotubes. The mechanisms EV biogenesis in the remain poorly understood, although studies Eukarya indicate that regulation lipid composition plays a major role initiating membrane curvature. EVs increasingly recognized important mediators intercellular communication via transfer wide variety molecular cargoes. They have been implicated many aspects cell physiology such stress response, competition, lateral gene (via RNA DNA), pathogenicity detoxification. Their various human pathologies aging has aroused much interest recent years. can be used decoys against viral attack but virus-infected cells also boost infection. Here, we review current knowledge on life their interactions world.

Language: Английский

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HIF-1 regulates CD47 expression in breast cancer cells to promote evasion of phagocytosis and maintenance of cancer stem cells

Proceedings of the National Academy of Sciences, Journal Year: 2015, Volume and Issue: 112(45)

Published: Oct. 28, 2015

Increased expression of CD47 has been reported to enable cancer cells evade phagocytosis by macrophages and promote the stem cell phenotype, but molecular mechanisms regulating have not determined. Here we report that hypoxia-inducible factor 1 (HIF-1) directly activates transcription gene in hypoxic breast cells. Knockdown HIF activity or increased bone marrow-derived macrophages. was mammosphere cultures, which are enriched for cells, deficiency led depletion. Analysis datasets derived from thousands patients with revealed correlated target patient mortality. Thus, contributes lethal phenotype is mediated HIF-1.

Language: Английский

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Extracellular vesicle isolation methods: rising impact of size-exclusion chromatography

Cellular and Molecular Life Sciences, Journal Year: 2019, Volume and Issue: 76(12), P. 2369 - 2382

Published: March 19, 2019

Language: Английский

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Macrophages derived exosomes deliver miR-223 to epithelial ovarian cancer cells to elicit a chemoresistant phenotype

Journal of Experimental & Clinical Cancer Research, Journal Year: 2019, Volume and Issue: 38(1)

Published: Feb. 15, 2019

How exosomal microRNAs (miRNAs) derived from macrophages contribute to the development of drug resistance in context hypoxic tumor microenvironment epithelial ovarian cancer (EOC) remains poorly understood.The miRNA levels were detected by qRT-PCR. Protein HIF-1α, CD163 and PTEN-PI3K/AKT pathway assessed Western blot (WB) Immunohistochemistry (IHC). Exosomes isolated, then confirmed Transmission electron microscopy (TEM), Nanoparticle Tracking Analysis (NTA) WB. Internalization macrophages-secreted exosomes EOC cells was Confocal microscope. Subsequently, Dual-luciferase reporter assay verified PTEN target miR-223. Gain- loss-of-function experiments, rescue SKOV3 xenograft models performed uncover underlying mechanisms miR-223 pathway, as well inducing multidrug vitro vivo.Here, we showed triggered recruitment induced into a tumor-associated macrophage (TAM)-like phenotype; enhanced malignant phenotype cells, enriched released under hypoxia, which could be transferred co-cultivated accompanied resistant cells. Besides, results functional revealed that promoted via both vivo vitro. Furthermore, patients with high HIF-1a expression had statistically higher CD163+ cell infiltration intertumoral Finally, circulating closely related recurrence EOC.These data indicate unique role cross-talk between chemotherapy resistance, through novel miR-223/PTEN-PI3K/AKT signaling pathway.

Language: Английский

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Hypoxia Inducible Factor-1α Potentiates Jagged 1-Mediated Angiogenesis by Mesenchymal Stem Cell-Derived Exosomes

Stem Cells, Journal Year: 2017, Volume and Issue: 35(7), P. 1747 - 1759

Published: April 5, 2017

Insufficient vessel growth associated with ischemia remains an unresolved issue in vascular medicine. Mesenchymal stem cells (MSCs) have been shown to promote angiogenesis via a mechanism that is potentiated by hypoxia. Overexpression of hypoxia inducible factor (HIF)-1α MSCs improves their therapeutic potential inducing transplanted tissues. Here, we studied the contribution exosomes released HIF-1α-overexpressing donor (HIF-MSC) endothelial cells. Exosome secretion was enhanced HIF-MSC. Omics analysis miRNAs and proteins incorporated into pointed Notch pathway as candidate mediator exosome communication. Interestingly, found Jagged1 sole ligand packaged MSC more abundant HIF-MSC than controls. The addition Jagged1-containing from cultures triggered transcriptional changes target genes induced vitro model capillary-like tube formation, both processes were stimulated HIF-1α. Finally, subcutaneous injection Jagged 1-containing Matrigel plug assay vivo, which robust when they derived cultures. All Jagged1-mediated effects could be blocked prior incubation anti-Jagged 1 antibody. together, results indicate stably overexpressing HIF-1α increased angiogenic capacity part increase packaging Jagged1, applications for treatment ischemia-related disease. Stem Cells 2017;35:1747-1759.

Language: Английский

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Versatile roles of extracellular vesicles in cancer

Journal of Clinical Investigation, Journal Year: 2016, Volume and Issue: 126(4), P. 1163 - 1172

Published: March 13, 2016

Numerous studies have shown that non-cell-autonomous regulation of cancer cells is an important aspect tumorigenesis. Cancer need to communicate with stromal by humoral factors such as VEGF, FGFs, and Wnt in order survive. Recently, extracellular vesicles (EVs) also been be involved cell-cell communication between the surrounding microenvironment for development cancer. In addition, these EVs contain small noncoding RNAs, including microRNAs (miRNAs), which contribute malignancy cells. Here, we provide overview current research on EVs, especially miRNAs EVs. We propose strategies treat cancers targeting around

Language: Английский

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Extracellular vesicles as tools and targets in therapy for diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 5, 2024

Abstract Extracellular vesicles (EVs) are nano-sized, membranous structures secreted into the extracellular space. They exhibit diverse sizes, contents, and surface markers ubiquitously released from cells under normal pathological conditions. Human serum is a rich source of these EVs, though their isolation proteins non-EV lipid particles poses challenges. These transport various cellular components such as proteins, mRNAs, miRNAs, DNA, lipids across distances, influencing numerous physiological events, including those within tumor microenvironment (TME). Their pivotal roles in communication make EVs promising candidates for therapeutic agents, drug delivery systems, disease biomarkers. Especially cancer diagnostics, EV detection can pave way early identification offers potential diagnostic Moreover, subtypes emerging targeted tools, highlighting clinical significance. The need non-invasive biomarkers to monitor biological processes purposes remains unfulfilled. Tapping unique composition could unlock advanced avenues future. In this review, we discuss detail conditions, cancers (encompassing head neck, lung, gastric, breast, hepatocellular carcinoma), neurodegenerative disorders, diabetes, viral infections, autoimmune renal diseases, emphasizing advancements molecular diagnostics delivery.

Language: Английский

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