scholarly journals Extracellular Vesicles in Tumors: A Potential Mediator of Bone Metastasis

2021 ◽  
Vol 9 ◽  
Author(s):  
Shenglong Li ◽  
Wei Wang
Keyword(s):  
Bone Metastasis ◽  
Extracellular Vesicles ◽  
Lipid Membrane ◽  
Bone Cells ◽  
Membrane Vesicles ◽  
Metastatic Tumor ◽  
Cell Types ◽  
Biological Phenomena ◽  
Breast And Prostate Cancer ◽  
Metastatic Sites

As one of the most common metastatic sites, bone has a unique microenvironment for the growth and prosperity of metastatic tumor cells. Bone metastasis is a common complication for tumor patients and accounts for 15–20% of systemic metastasis, which is only secondary to lung and liver metastasis. Cancers prone to bone metastasis include lung, breast, and prostate cancer. Extracellular vesicles (EVs) are lipid membrane vesicles released from different cell types. It is clear that EVs are associated with multiple biological phenomena and are crucial for intracellular communication by transporting intracellular substances. Recent studies have implicated EVs in the development of cancer. However, the potential roles of EVs in the pathological exchange of bone cells between tumors and the bone microenvironment remain an emerging area. This review is focused on the role of tumor-derived EVs in bone metastasis and possible regulatory mechanisms.

scholarly journals On the Choice of the Extracellular Vesicles for Therapeutic Purposes

2019 ◽  
Vol 20 (2) ◽  
pp. 236 ◽  
Author(s):  
Claudia Campanella ◽  
Celeste Caruso Bavisotto ◽  
Mariantonia Logozzi ◽  
Antonella Marino Gammazza ◽  
Davide Mizzoni ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Lipid Membrane ◽  
Cell Communication ◽  
Membrane Vesicles ◽  
Free Form ◽  
Target Cells ◽  
Disease Biomarkers ◽  
Cellular Source ◽  
Therapeutic Molecules

Extracellular vesicles (EVs) are lipid membrane vesicles released by all human cells and are widely recognized to be involved in many cellular processes, both in physiological and pathological conditions. They are mediators of cell-cell communication, at both paracrine and systemic levels, and therefore they are active players in cell differentiation, tissue homeostasis, and organ remodeling. Due to their ability to serve as a cargo for proteins, lipids, and nucleic acids, which often reflects the cellular source, they should be considered the future of the natural nanodelivery of bio-compounds. To date, natural nanovesicles, such as exosomes, have been shown to represent a source of disease biomarkers and have high potential benefits in regenerative medicine. Indeed, they deliver both chemical and bio-molecules in a way that within exosomes drugs are more effective that in their exosome-free form. Thus, to date, we know that exosomes are shuttle disease biomarkers and probably the most effective way to deliver therapeutic molecules within target cells. However, we do not know exactly which exosomes may be used in therapy in avoiding side effects as well. In regenerative medicine, it will be ideal to use autologous exosomes, but it seems not ideal to use plasma-derived exosomes, as they may contain potentially dangerous molecules. Here, we want to present and discuss a contradictory relatively unmet issue that is the lack of a general agreement on the choice for the source of extracellular vesicles for therapeutic use.

Abstract 432: Endothelial Cells Express miR-33a-5p and Release Extracellular Vesicles Containing miR-33a-5p

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Alexis Stamatikos ◽  
Lucia Vojtech ◽  
Nagadhara Dronadula ◽  
David Dichek
Keyword(s):  
Electron Microscopy ◽  
Endothelial Cells ◽  
Extracellular Vesicles ◽  
Small Rna ◽  
Cholesterol Efflux ◽  
Lipid Membrane ◽  
Cell Types ◽  
Blue Staining ◽  
Coomassie Blue Staining ◽  
Coomassie Blue

Background: The microRNA miR-33a-5p increases cellular cholesterol by posttranscriptional silencing of genes involved in cholesterol efflux. Previous studies showed that miR-33a-5p inhibition protects against atherosclerosis. Atheroprotective effects of miR-33a-5p inhibition are attributed to actions in hepatocytes that raise plasma HDL and actions in macrophages that enhance cholesterol efflux. We hypothesized that miR-33a-5p is also expressed in primary arterial endothelial cells (EC) and that miR-33a-5p might contribute to atherosclerosis by promoting cholesterol accumulation in EC. We also hypothesized that EC could release miR-33a-5p in extracellular vesicles (EV; including exosomes and microvesicles) that transferred miR-33a-5p to neighboring vascular cells such as SMC and macrophages, inhibiting cholesterol efflux, promoting lipid accumulation in these cells, and accelerating atherosclerosis. Methods: We cultured bovine aortic endothelial cells (BAEC) in serum-free medium, collected the medium, and isolated EV by ultracentrifugation. To test whether we had isolated EV, we compared EV and BAEC lysates by SDS-PAGE, Coomassie blue staining, and immunoblotting. We measured EV size with nanoparticle tracking analysis and imaged the particles with transmission electron microscopy. We extracted total RNA from BAEC and EV, measured RNA size using BioAnalyzer, and detected miR-33a-5p expression using RT-PCR and restriction digestion as well as qRT-PCR. Results: Coomassie blue staining revealed large differences between BAEC and EV lysates. The exosome marker CD9 was present at higher levels in EV lysate compared to BAEC lysate. Most of the EV were in the size range of exosomes, and appeared as typical lipid membrane-bound spheres by electron microscopy. EV contained primarily small RNA (~25-200 nucleotides). miR-33a-5p was detected both in BAEC lysates and in detergent-soluble EV. Conclusions: Primary arterial EC express miR-33a-5p and release EV rich in small RNA, including miR-33a-5p. Manipulating miR-33a-5p expression in EC, for example with a miR-33a-5p antagomiR, may be an effective therapeutic approach for increasing cholesterol efflux from multiple vessel wall cell types and preventing/reversing atherosclerosis.

scholarly journals Urinary Biomarkers in Bladder Cancer: Where Do We Stand and Potential Role of Extracellular Vesicles

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1400 ◽  
Author(s):  
Manuel Castanheira de Oliveira ◽  
Hugo R. Caires ◽  
Maria J. Oliveira ◽  
Avelino Fraga ◽  
M. Helena Vasconcelos ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Immune Escape ◽  
Membrane Vesicles ◽  
Diagnostic Procedures ◽  
Cell Types ◽  
Therapy Resistance ◽  
Great Promise ◽  
Low Grade

Extracellular vesicles (EVs) are small membrane vesicles released by all cells and involved in intercellular communication. Importantly, EVs cargo includes nucleic acids, lipids, and proteins constantly transferred between different cell types, contributing to autocrine and paracrine signaling. In recent years, they have been shown to play vital roles, not only in normal biological functions, but also in pathological conditions, such as cancer. In the multistep process of cancer progression, EVs act at different levels, from stimulation of neoplastic transformation, proliferation, promotion of angiogenesis, migration, invasion, and formation of metastatic niches in distant organs, to immune escape and therapy resistance. Moreover, as products of their parental cells, reflecting their genetic signatures and phenotypes, EVs hold great promise as diagnostic and prognostic biomarkers. Importantly, their potential to overcome the current limitations or the present diagnostic procedures has created interest in bladder cancer (BCa). Indeed, cystoscopy is an invasive and costly technique, whereas cytology has poor sensitivity for early staged and low-grade disease. Several urine-based biomarkers for BCa were found to overcome these limitations. Here, we review their potential advantages and downfalls. In addition, recent literature on the potential of EVs to improve BCa management was reviewed and discussed.

scholarly journals Extracellular Vesicles in Bone Metastasis: Key Players in the Tumor Microenvironment and Promising Therapeutic Targets

2020 ◽  
Vol 21 (18) ◽  
pp. 6680 ◽  
Author(s):  
Takaaki Tamura ◽  
Yusuke Yoshioka ◽  
Shinichi Sakamoto ◽  
Tomohiko Ichikawa ◽  
Takahiro Ochiya
Keyword(s):  
Bone Metastasis ◽  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Novel Treatments ◽  
Biological Phenomena ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Extracellular vesicles (EVs) are lipid membranous vesicles that are released from every type of cell. It has become clear that EVs are involved in a variety of biological phenomena, including cancer progression, and play critical roles in intracellular communication through the horizontal transfer of cellular cargoes such as proteins, DNA fragments, RNAs including mRNA and non-coding RNAs (microRNA, piRNA, and long non-coding RNA) and lipids. The most common cause of death associated with cancer is metastasis. Recent investigations have revealed that EVs are deeply associated with metastasis. Bone is a preferred site of metastasis, and bone metastasis is generally incurable and dramatically affects patient quality of life. Bone metastasis can cause devastating complications, including hypercalcemia, pathological fractures, spinal compression, and bone pain, which result in a poor prognosis. Although the mechanisms underlying bone metastasis have yet to be fully elucidated, increasing evidence suggests that EVs in the bone microenvironment significantly contribute to cancer progression and cancer bone tropism. Emerging evidence on EV functions in bone metastasis will facilitate the discovery of novel treatments. In this review, we will discuss the remarkable effects of EVs, especially on the tumor microenvironment in bone.

scholarly journals Mechanisms, Diagnosis and Treatment of Bone Metastases

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2944
Author(s):  
Jozef Ban ◽  
Valerie Fock ◽  
Dave N. T. Aryee ◽  
Heinrich Kovar
Keyword(s):  
Bone Marrow ◽  
Bone Metastases ◽  
Tumor Cells ◽  
Metastatic Tumor ◽  
Disease Outcome ◽  
Bone Marrow Niche ◽  
Therapeutic Implications ◽  
Metastatic Process ◽  
Breast And Prostate Cancer ◽  
Metastatic Sites

Bone and bone marrow are among the most frequent metastatic sites of cancer. The occurrence of bone metastasis is frequently associated with a dismal disease outcome. The prevention and therapy of bone metastases is a priority in the treatment of cancer patients. However, current therapeutic options for patients with bone metastatic disease are limited in efficacy and associated with increased morbidity. Therefore, most current therapies are mainly palliative in nature. A better understanding of the underlying molecular pathways of the bone metastatic process is warranted to develop novel, well-tolerated and more successful treatments for a significant improvement of patients’ quality of life and disease outcome. In this review, we provide comparative mechanistic insights into the bone metastatic process of various solid tumors, including pediatric cancers. We also highlight current and innovative approaches to biologically targeted therapy and immunotherapy. In particular, we discuss the role of the bone marrow microenvironment in the attraction, homing, dormancy and outgrowth of metastatic tumor cells and the ensuing therapeutic implications. Multiple signaling pathways have been described to contribute to metastatic spread to the bone of specific cancer entities, with most knowledge derived from the study of breast and prostate cancer. However, it is likely that similar mechanisms are involved in different types of cancer, including multiple myeloma, primary bone sarcomas and neuroblastoma. The metastatic rate-limiting interaction of tumor cells with the various cellular and noncellular components of the bone-marrow niche provides attractive therapeutic targets, which are already partially exploited by novel promising immunotherapies.

Small extracellular vesicles from epicardial fat of patients with atrial fibrillation induce inflammation, fibrosis and re-entrant arrhythmias

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
O Shaihov-Teper ◽  
E Ram ◽  
R Brzezinski ◽  
D Volvovitch ◽  
E Zuroff ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Extracellular Vesicles ◽  
Heart Surgery ◽  
Open Heart Surgery ◽  
Induced Pluripotent Stem Cell ◽  
Membrane Vesicles ◽  
Cell Types ◽  
Size Exclusion ◽  
Epicardial Fat ◽  
Atrial Remodeling

Abstract Background and aim Epicardial fat (eFat) has been linked to atrial remodeling and fibrillation (AF). Small extracellular vesicles (sEVs) are heterogeneous membrane vesicles released by all cell types. They can both protect and damage tissues by the delivery of multiple different messengers. Surprisingly, the role of sEVs in the pathogenesis of AF has not been studied. Thus, we aimed to determine whether sEVs derived from eFat play a role in the pathogenesis of AF. Methods and results We collected eFat specimens from patients with and without chronic or paroxysmal AF undergoing open-heart surgery. Isolated eFat specimens were cut into small pieces and incubated as organ cultures. We isolated sEVs from the medium of the explant by differential ultra-centrifugation, high-density gradient or size exclusion chromatography (SEC), and characterized vesicle size distribution, morphology, specific markers, histology and molecular cargo. Immunostaining for macrophage accumulation, fibrosis and apoptosis confirmed the pro-inflammatory and pro-fibrotic properties of eFat sEVs from patients with AF (Fig. 1). eFat sEVs labeled with PKH26 were massively up taken by endothelial cells (Fig. 2). Real-time PCR showed an increased level of oxidative stress genes in endothelial cells. eFat sEVs from patients with AF caused more fibrosis after injection into rat hearts than those without AF. (Fig. 3). Finally, while eFat sEVs from patients with and without AF induced shorter action potential duration, only eFat sEVs from patients with AF induced sustained re-entry (rotor) in human induced pluripotent stem cell (iPS)-derived cardiomyocytes (Fig. 4) Conclusion We show, for the first time, that sEVs from eFat of patients with AF demonstrate unique pro-inflammatory, pro-fibrotic and pro-arrhythmic properties. Our findings suggest that eFat sEVs can induce cellular, molecular and electrophysiological remodeling that can subsequently lead to the development of AF. Funding Acknowledgement Type of funding source: None

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.

On the Interplay of Extracellular Vesicles and Viral Infections

2020 ◽  
Vol 2 (1) ◽  
pp. 14-27
Author(s):  
Christoph Metzner ◽  
Marianne Zaruba
Keyword(s):  
Extracellular Vesicles ◽  
Lipid Membrane ◽  
Viral Infections ◽  
Membrane Vesicles ◽  
Enveloped Virus ◽  
Viral Particles ◽  
Potential Applications ◽  
Definition Of ◽  
Relationship Of ◽  
The Relationship

A broad definition of extracellular vesicles – lipid membrane enclosed vesicles of a given size range, produced by cells into the surrounding media and unable to replicate independently – does not only apply to exosomes or microvesicles produced by eukaryotic cells, outer membrane or outer-inner membrane vesicles produced by gram-negative bacteria and membrane vesicles produced by gram-positive bacteria (and archaea), but also extends to enveloped virus particles. They share biophysical and biochemical characteristics as well as functional properties, making it a challenge to distinguish between types of vesicles. In this review, we will briefly introduce different extracellular vesicles before concentrating on the relationship of viral particles to extracellular vesicles, taking practical issues into consideration as well as molecular interactions and the subsequent effects on infectivity and pathogenesis. Finally, we will briefly discuss potential applications of the relationship between extracellular vesicles and viral particles.

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 Two Small Extracellular Vesicle sRNAs Derived From Mycobacterium tuberculosis Serve as Diagnostic Biomarkers for Active Pulmonary Tuberculosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Geng Lu ◽  
XinRui Jiang ◽  
Anni Wu ◽  
Jiawei Zhou ◽  
Hengjun Liu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Extracellular Vesicles ◽  
Small Rna ◽  
Membrane Vesicles ◽  
Cell Types ◽  
Extracellular Vesicle ◽  
Diagnostic Biomarkers ◽  
Tuberculosis Patients ◽  
Active Pulmonary Tuberculosis ◽  
Novel Approach

The rapid diagnosis of tuberculosis (TB) is of great significance for the control and treatment of TB. However, TB remains a major healthy, social, and economic burden worldwide because of the lack of ideal diagnostic biomarkers. Mycobacterium tuberculosis (M. tuberculosis)-encoded small RNA (sRNA) is a class of regulation small RNA. Several studies have identified M. tuberculosis encoded-sRNAs in the serum/plasm of M. tuberculosis-infected patients. Small extracellular vesicles are small membrane vesicles secreted by many cell types during physiological and pathological conditions. Recent evidence has indicated that most of the nucleic acids in the serum/plasma are packaged in the small extracellular vesicles and could serve as ideal diagnostic biomarkers. In this study, we attempted a novel approach for TB diagnosis: targeting small extracellular vesicles M. tuberculosis encoded sRNA (sRNA) by qRT-PCR. The results showed that M. tuberculosis-encoded ASdes and MTB-miR5 only existed in tuberculosis patients and have the potential to serve as a sensitive and accurate methodology for TB diagnosis.

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