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Exosomes play a role in multiple myeloma bone disease and tumor development by targeting osteoclasts and osteoblasts.

Progression of multiple myeloma (MM) is largely dependent on the bone marrow (BM) microenvironment wherein communication through different factors including extracellular vesicles takes place. This cross-talk not only leads to drug resistance but also to the development of osteolysis. Targeting vesicle secretion could therefore simultaneously ameliorate drug response and bone disease. In this paper, we examined the effects of MM exosomes on different aspects of osteolysis using the 5TGM1 murine model. We found that 5TGM1 sEVs, or 'exosomes', not only enhanced osteoclast activity, they also blo

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… Exosomes are small EVs, formed inside multivesicular bodies (MVB) and are actively secreted by the cell through fusion of the MVB with the cell membrane. Other EVs, such as microvesicles, are formed by a direct budding from the plasma membrane. They can range in size from 30–1000 nm. … Hepatitis E virus egress depends on the exosomal pathway, with secretory exosomes derived from multivesicular bodies. J. Gen. Virol. 2014;95:2166–2175. doi: 10.1099/vir.0.066910-0. 31. Matsumoto A, et al. …

Role of exosomes in pancreatic cancer.

Pancreatic cancer is one of the most lethal malignancies. Exosomes, which are released by multiple cell types, such as cancer cells, contain functional biomolecules (including proteins, nucleic acids and lipids) that can be horizontally delivered to recipient cells. Exosomes act as the most prominent mediator of intercellular communication and can regulate, instruct and re-educate their surrounding microenvironment and target specific organs. The present review performed an extensive search of multiple databases from 2005 to April 23 2017, for eligible literature relating to exosomes and their

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… Exosomes (30–150 nm in diameter) are extracellular vesicles generated by the inward budding of the membrane (endocytosis), which leads to the subsequent formation of multivesicular bodies and their release by exocytosis. … Thus, on their membranes, exosomes express a variety of markers of multivesicular bodies, such as tetraspanins. …

Nanotherapeutics in the EU: an overview on current state and future directions.

The application of nanotechnology in areas of drug delivery and therapy (ie, nanotherapeutics) is envisioned to have a great impact on public health. The ability of nanotherapeutics to provide targeted drug delivery, improve drug solubility, extend drug half-life, improve a drug's therapeutic index, and reduce a drug's immunogenicity has resulted in the potential to revolutionize the treatment of many diseases. In this paper, we review the liposome-, nanocrystal-, virosome-, polymer therapeutic-, nanoemulsion-, and nanoparticle-based approaches to nanotherapeutics, which represent the most suc

Exosomes to exosome-functionalized scaffolds: a novel approach to stimulate bone regeneration.

Bone regeneration is a complex biological process that relies on the orchestrated interplay of various cellular and molecular events. Bone tissue engineering is currently the most promising method for treating bone regeneration. However, the immunogenicity, stable and cell quantity of seed cells limited their application. Recently, exosomes, which are small extracellular vesicles released by cells, have been found to effectively address these problems and better induce bone regeneration. Meanwhile, a growing line of research has shown the cargos of exosomes may provide effective therapeutic an

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… Exosomes, with diameters ranging from 30 to 150 nm extracellular vesicles (EVs), originate from the endosomal system, specifically as intraluminal vesicles (ILVs) within multivesicular bodies (MVBs). … Biosynthesis of exosomes involves sorting cargo molecules into intracavicular vesicles (ILV) in endosomal compartments, which then mature into multivesicular bodies (MVBs). …

Non-Exosomal and Exosomal Circulatory MicroRNAs: Which Are More Valid as Biomarkers?

MicroRNAs (miRNAs) are a group of small non-coding RNAs with approximately 19-25 nucleotides that are involved in regulating a range of developmental and physiological processes. Non-exosomal circulating and exosomal miRNAs have also been proposed to be useful in diagnostics as biomarkers for diseases and different types of cancer. In this review, the quantity of miRNAs and of reliable experimental data analyses of miRNAs that come from exosomal and non-exosomal sources are discussed from the perspective of their use as biomarkers for cancer and other diseases, including viral infections, nerv

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… Exosomes are small intraluminal vesicles derived from the exocytosis of multivesicular bodies (MVBs) with plasma membrane ( Kosaka et al., 2010 ; Kim et al., 2017 ). Specifically, the biogenesis of exosomes starts with the internalization of parental cell membrane to produce endosomes. … These endosomes with small vesicles inside them are called multivesicular bodies (MVBs). MVBs or late endosomes later fuse with parental cell membrane to release the intraluminal endosomal vesicles into the extracellular environment to become exosomes ( Zhang et al., 2015 ). …

Chemotherapy-Induced Tissue Injury: An Insight into the Role of Extracellular Vesicles-Mediated Oxidative Stress Responses.

The short- and long-term side effects of chemotherapy limit the maximum therapeutic dose and impair quality of life of survivors. Injury to normal tissues, especially chemotherapy-induced cardiomyopathy, is an unintended outcome that presents devastating health impacts. Approximately half of the drugs approved by the Food and Drug Administration for cancer treatment are associated with the generation of reactive oxygen species, and Doxorubicin (Dox) is one of them. Dox undergoes redox cycling by involving its quinone structure in the production of superoxide free radicals, which are thought to

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… Exosomes are the smallest EVs (50–100 nm) and originate from the invagination of late endosomal membranes forming multiple intraluminal vesicles (ILVs) called multivesicular bodies (MVBs). Those ILVs become exosomes when they are released by the fusion of the MVB membrane with the plasma membrane. … Induction of autophagy promotes fusion of multivesicular bodies with autophagic vacuoles in k562 cells Traffic 2008 9 230 250 10.1111/j.1600-0854.2007.00677.x 17999726 51. Guo J.L. Lee V.M. Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases Nat. …

Exosomes in the Repair of Bone Defects: Next-Generation Therapeutic Tools for the Treatment of Nonunion.

Nonunion with bone defects, a common complication after long bone fracture, is a major challenge for orthopaedic surgeons worldwide because of the high incidence rate and difficulties in achieving successful treatment. Bone defects are the main complications of nonunion. The conventional biological treatments for nonunion with bone defects involve the use of autologous bone grafts or bone graft substitutes and cell-based therapy. Traditional nonunion treatments have always been associated with safety issues and various other complications. Bone grafts have limited autologous cancellous bone an

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… Firstly, endosomes are produced by plasma membrane internalization of donor cells, and then the proteins and RNAs (including lncRNAs, circRNAs, mRNAs, and miRNAs) are selectively crated into the multivesicular bodies, via endosomal sorting complex required for transport- (ESCRT-) dependent or ESCRT-independent … Subsequently, the multivesicular bodies are either fused to the lysosome for degradation or released into the extracellular space by fusion with the plasma membrane to produce exosomes. Microvesicles are produced directly on the plasma membrane {Tao, 2018 #264}. …

Sending the Signal to Bone: How Tumor-Derived EVs Orchestrate Pre-Metastatic Niche Formation and Skeletal Colonization.

Bone is a preferred site for disseminated tumor cells, yet the molecular mechanisms that prepare the skeletal microenvironment for metastatic colonization are only beginning to be understood. At the heart of this process are extracellular vesicles (EVs), nano-sized, lipid-encapsulated particles secreted by cancer cells and stromal components. This review consolidates current findings that position EVs as key architects of the bone-metastatic niche. We detail the biogenesis of EVs and their organotropic distribution, focusing on how integrin patterns and bone-specific ligands guide vesicle homi

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… The oxysterol metabolite 27-hydroxycholesterol further promotes EV release by preventing multivesicular bodies’ degradation in lysosomes [ 48 ]. … Dynamic Reorganization of Multivesicular Bodies and Exosome Production Impacted by Sonoporation Sci. Rep. 2024 14 27432 10.1038/s41598-024-79042-6 39521850 PMC11550812 27. Lyu C. Sun H. Sun Z. Liu Y. Wang Q. …

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

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.

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… More specifically, exosomes are formed by the inward budding of early endosomes to form multivesicular bodies (MVBs). These MVBs fuse with the limiting plasma membrane to release exosomes into the extracellular space. Microvesicles originate by direct shedding or budding from the plasma membrane. … Microvesicles and Vesicles of Multivesicular Bodies Versus “Virus-Like” Particles J. Natl. Cancer Inst. 1975 54 1137 1148 10.1093/jnci/54.5.1137 165305 6. Dvorak H.F. Quay S.C. Orenstein N.S. Dvorak A.M. Hahn P. Bitzer A.M. Carvalho A.C. …

Extracellular RNA in melanoma: Advances, challenges, and opportunities.

Melanoma, a malignant mass lesion that originates in melanocytes and has a high rate of malignancy, metastasis, and mortality, is defined by these characteristics. Malignant melanoma is a kind of highly malignant tumor that produces melanin and has a high mortality rate. Its incidence accounts for 1%-3% of all malignant tumors and shows an obvious upward trend. The discovery of biomolecules for the diagnosis and treatment of malignant melanoma has important application value. So far, the exact molecular mechanism of melanoma development relevant signal pathway still remains unclear. According

The Role of Extracellular Vesicles in Bone Metastasis.

Multiple types of cancer have the specific ability to home to the bone microenvironment and cause metastatic lesions. Despite being the focus of intense investigation, the molecular and cellular mechanisms that regulate the metastasis of disseminated tumor cells still remain largely unknown. Bone metastases severely impact quality of life since they are associated with pain, fractures, and bone marrow aplasia. In this review, we will summarize the recent discoveries on the role of extracellular vesicles (EV) in the regulation of bone remodeling activity and bone metastasis occurrence. Indeed,

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… Exosomes are small vesicles (50–100 nm) that are derived from multivesicular bodies (MVB), and are released by fusion of MVB with the cell membrane; microvesicles are larger vesicles (100 nm–1 µm) and are derived from budding of the plasma membrane; apoptotic vesicles have a size ranging from 1 to 5 … They are released constitutively and under specific stimuli, and derive from the fusion of multivesicular bodies (MVB) with the plasma membrane. MVB are formed during the maturation of early endosomes into late endosomes, due to the accumulation of intraluminal vesicles [ 34 ]. …

Recent Progress of Exosomes in Multiple Myeloma: Pathogenesis, Diagnosis, Prognosis and Therapeutic Strategies.

Multiple myeloma (MM) is a hematological malignancy that is still incurable. The bone marrow microenvironment (BMM), with cellular and non-cellular components, can create a favorable environment for the survival, proliferation and migration of MM cells, which is the main reason for the failure of MM therapies. Many studies have demonstrated that exosomes play an important role in the tumor-supportive BMM. Exosomes are nanoscale vesicles that can be released by various cells. Some exosomes contribute to the pathogenesis and progression of MM. MM-derived exosomes act on different cells in the BM

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… The accumulations of ILVs in the late endosomes are termed multivesicular bodies (MVBs). (3) The fusion of MVBs with the plasma membrane results in the release of ILVs, known as exosomes. [ 6 , 7 ]. … The accumulations of ILVs in the late endosomes are termed multivesicular bodies (MVBs). On the one hand, MVBs may fuse with lysosomes for degradation. …

Roles of Microvesicles in Tumor Progression and Clinical Applications.

Microvesicles are extracellular vesicles with diameter ranging from 100 to 1000 nm that are secreted by tumor cells or other cells in the tumor microenvironment. A growing number of studies demonstrate that tumor-derived microvesicles are involved in tumor initiation and progression, as well as drug resistance. In addition, tumor-derived microvesicles carry a variety of immunogenic molecules and inhibit tumor response to immunotherapy; therefore, they can be exploited for use in tumor vaccines. Moreover, because of their high stability, tumor-derived microvesicles extracted from body fluids ca

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… Table 2 Distinctions Among Microvesicles, Exosomes, Oncosomes, and Apoptotic Bodies (Classification of Extracellular Vesicles) Vesicle Type Microvesicles Exosomes Oncosomes Apoptotic Bodies Origin Plasma membrane Multivesicular bodies (MVBs) Plasma membrane Plasma membrane Biogenesis Shedding from the … bodies (MVBs). …

The emerging role of exosomes in innate immunity, diagnosis and therapy.

Exosomes, which are nano-sized transport bio-vehicles, play a pivotal role in maintaining homeostasis by exchanging genetic or metabolic information between different cells. Exosomes can also play a vital role in transferring virulent factors between the host and parasite, thereby regulating host gene expression and the immune interphase. The association of inflammation with disease development and the potential of exosomes to enhance or mitigate inflammatory pathways support the notion that exosomes have the potential to alter the course of a disease. Clinical trials exploring the role of exo

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… The fusion of multivesicular bodies with the plasma membrane results in the release of intraluminal vesicles into the extracellular space, giving rise to “exosomes” ( 2 , 8 , 9 ). This is primarily an endosomal sorting complex required for transport (ESCRT)-dependent processes. … Hijacking multivesicular bodies enables long-term and exosome-mediated long-distance action of anthrax toxin . Cell Rep ( 2013 ) 5 : 986–96 . doi: 10.1016/j.celrep.2013.10.019 PMC3866279 24239351 42 Keller MD Ching KL Liang F-X Dhabaria A Tam K Ueberheide BM . …

Extracellular Vesicles in Tumors: A Potential Mediator of Bone Metastasis.

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 transportin

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… Generation, Composition, and Major Biological Functions of Extracellular Vesicles The formation of EVs mainly involves four processes, including sprouting, invagination, multivesicular body formation, and secretion ( Mathew et al., 2020 ; Zhang Y. et al., 2020 ). EVs are generated in endosomes. … Invagination of the cell membrane results in the formation of early endosomes, and late endosomes sprout inward to form luminal vesicles that are transformed into multivesicular bodies (MVBs) with multiple small vesicles. …

Emerging Roles of Mesenchymal Stem/Stromal-Cell-Derived Extracellular Vesicles in Cancer Therapy.

Despite the tremendous efforts of many researchers and clinicians, cancer remains the second leading cause of mortality worldwide. Mesenchymal stem/stromal cells (MSCs) are multipotent cells residing in numerous human tissues and presenting unique biological properties, such as low immunogenicity, powerful immunomodulatory and immunosuppressive capabilities, and, in particular, homing abilities. Therapeutic functions of MSCs are mediated mostly by the paracrine effect of released functional molecules and other variable components, and among them the MSC-derived extracellular vesicles (MSC-EVs)

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… Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies. Biochimie. 2007;89:205–212. doi: 10.1016/j.biochi.2006.10.014. 53. Kalra H., Drummen G.P.C., Mathivanan S. Focus on Extracellular Vesicles: Introducing the Next Small Big Thing. Int. J. Mol. …

A Challenge to Aging Society by microRNA in Extracellular Vesicles: microRNA in Extracellular Vesicles as Promising Biomarkers and Novel Therapeutic Targets in Multiple Myeloma.

Multiple myeloma (MM) is a malignancy of terminally differentiated plasma cells and is the second most common hematological cancer. MM frequently occurs in the elderly population with the median age as the middle sixties. Over the last 10 years, the prognosis of MM has been dramatically improved by new therapeutic drugs; however, MM is still incurable. The pathogenesis of MM is still unclear, thus greater understanding of the molecular mechanisms of MM malignancy is desirable. Recently, microRNAs (miRNAs) were shown to modulate the expression of genes critical for MM pathogenesis. In addition,

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… Exosomes are initially formed by a process of inward budding in early endosomes to form multivesicular bodies [ 3 , 4 ]. … Exosome: From internal vesicle of the multivesicular body to intercellular signaling device. J. Cell Sci. 2000;19:3365–3374. doi: 10.1242/jcs.113.19.3365. 2. Raposo G., Stoorvogel W. Extracellular vesicles: Exosomes, microvesicles, and friends. J. …

A review on the current literature regarding the value of exosome miRNAs in various diseases.

Exosome microRNAs (miRNAs) have great research outlook in clinical therapy and biomarkers, they have been found to have a close to multiple diseases. A growing number of studies have attempted to alleviate or treat diseases through exosomes. It indicates that miRNAs in exosomes have great significance in preventing and controlling diseases in clinical research. We summarise these studies below to better understand their implications.We screened and analyzed more than 100 articles from PubMed, Web of Science, and other databases from 1987 to 2022. Data of the clinical trials are collected from

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… ILVs contain many types of vesicular structures, and their mature bodies are called multivesicular bodies (MVBs). MVBs can be degraded and self-cleared through lysosomes and undergo apoptosis to ensure homeostasis. … The cell membrane invaginates to form early endosomes, which further mature and eventually form multivesicular bodies (MVBs). Some of the MVBs are degraded by lysosomes while the other MVBs fuse with the cell membrane and release the exosomes. …

Platelet proteome and tumor dormancy: can platelets content serve as predictive biomarkers for exit of tumors from dormancy?

Although tumor dormancy is highly prevalent, the underling mechanisms are still mostly unknown. It is unclear which lesions will progress and become a disseminated cancer, and which will remain dormant and asymptomatic. Yet, an improved ability to predict progression would open the possibility of timely treatment and improvement in outcomes. We have recently described the ability of platelets to selectively uptake angiogenesis regulators very early in tumor growth, and proposed their use as an early marker of malignancy. In this review we will summarize current knowledge about these processes

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… The formation of alpha-granules is poorly understood, and is thought to involve recently described multivesicular bodies [ 65 ]. While an attractive target for future modulation of platelet content, the process has not been sufficiently understood. … Multivesicular bodies are an intermediate stage in the formation of platelet alpha-granules. Blood. 1998;91:2313–2325. 66. Ma L., Hollenberg M.D., Wallace J.L. Thrombin-induced platelet endostatin release is blocked by a proteinase activated receptor-4 (PAR4) antagonist. Br. J. …

Extracellular Vesicles in Chronic Lymphocytic Leukemia: Tumor Microenvironment Messengers as a Basis for New Targeted Therapies?

In addition to intrinsic genomic and nongenomic alterations, tumor progression is also dependent on the tumor microenvironment (TME, mainly composed of the extracellular matrix (ECM), secreted factors, and bystander immune and stromal cells). In chronic lymphocytic leukemia (CLL), B cells have a defect in cell death; contact with the TME in secondary lymphoid organs dramatically increases the B cells' survival via the activation of various molecular pathways, including the B cell receptor and CD40 signaling. Conversely, CLL cells increase the permissiveness of the TME by inducing changes in th

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… EVs were initially separated into two main categories [ 28 , 31 ]: - Exosomes (EXOs) are 30–150 nm vesicles generated through endosome maturation, the formation of multivesicular bodies (MVBs), intraluminal vesicles, and the fusion of MVBs with the plasma membrane. … body; NF-κB—nuclear factor kappa B; NK—natural killer; PB—peripheral blood; PD-L1—programmed death ligand 1; PD-1—programmed death 1; PI3K—phosphoinositide 3-kinase; RS—Richter syndrome; SDF-1—stromal cell-derived factor 1; SYK—spleen tyrosine kinase; TLR—toll-like receptor; TME—tumor microenvironment …