Search Results (518)

Ovarian cancer (OC) remains the most lethal gynecological malignancy, mostly due to its frequent diagnosis at advanced stages, early peritoneal dissemination, ascites formation, and limited sensitivity of currently available approaches for early detection. Extracellular vesicles (EVs), particularly exosomes, mediate intercellular communication through the transfer of proteins, lipids, metabolites, and nucleic acids. In OC, EV-associated protein profiles reflect both tumor-cell-intrinsic programs and the complex interactions between malignant cells and the peritoneal microenvironment. This review summarizes current evidence regarding the involvement of exosomal proteins in OC progression, with particular emphasis on epithelial–mesenchymal transition, mesothelial reprogramming, extracellular matrix remodeling, angiogenesis, immune suppression, peritoneal dissemination, and platinum resistance. Mechanistic studies indicate that exosomal proteins, including CD44, the integrin α5β1/asparaginyl endopeptidase complex, annexin A2, low-density lipoprotein receptor-related protein 1, and programmed death-ligand 1, can directly contribute to metastatic niche formation and tumor progression. In parallel, proteomic studies of plasma-, serum-, ascites-, peritoneal-fluid-, and uterine-lavage-derived EVs have identified candidate liquid-biopsy biomarkers, including MUC1, EpCAM, FOLR1, integrins, complement- and coagulation-related proteins, and proteins associated with treatment resistance. To integrate the biological significance of proteins reported in OC-associated exosomes, we additionally performed protein–protein interaction and functional enrichment analyses. These analyses revealed interconnected protein groups associated with cell adhesion, oxidative stress adaptation, secretory remodeling, lipid metabolism, extracellular matrix organization, and inflammatory signaling. Taken together, the available evidence supports exosomal proteome profiling as a promising approach for investigating OC dissemination and developing minimally invasive diagnostic and prognostic tools. However, standardized EV isolation, quantitative proteomics, functional validation, and independent clinical cohorts remain essential for translation into clinical practice. Full article

Exosomes are small extracellular vesicles that mediate intercellular communication and, in cancer, carry cargo that both reflects the donor tumor cell and influences recipient cells within local and distant microenvironments. Exosomal proteins and microRNAs have been reported individually across many cancer types, but rarely compared on a common basis; in this review, previously reported molecules from eight cancer categories—blood, breast, colon, kidney, liver, lung, prostate, and stomach—were compiled from curated repositories and re-analyzed within a single functional framework. In total, 3643 exosomal proteins (523 hematologic, 3120 solid-tumor) and 627,225 miRNA–target pairs, derived from 350 unique microRNAs, were organized using Gene Ontology, KEGG, and PANTHER annotation. Across cancers, proteins converged on a reproducible core—signaling, transport, cytoskeletal organization, and extracellular interaction—dominated by binding, catalytic, and transporter functions localized to membrane, vesicle, and extracellular compartments. Comparisons between hematologic and solid malignancies revealed both shared cancer-associated functions and context-dependent patterns linked to tissue origin and disease ecology. Together, these findings indicate that integrated protein-and-microRNA profiling offers a useful framework for understanding tumor communication, refining cancer classification, and advancing biomarker discovery, while underscoring that harmonized workflows, independent validation, and mechanistic follow-up remain necessary before descriptive enrichment outputs can support clinically robust applications. Full article

The nuclear RNA exosome, a conserved 3′→5′ ribonuclease complex, degrades the vast majority of RNA polymerase II output, including promoter upstream transcripts, enhancer RNAs, antisense transcripts, and retrotransposon-derived RNAs. Beyond this housekeeping role, the exosome acts as an epigenetic effector, and its dysfunction underlies a growing spectrum of human disease. Here we integrate recent structural, genomic, and disease-focused studies into a unified model of the exosome as a guardian of the epigenome. We describe how MTR4-containing adaptor complexes TRAMP, NEXT, and PAXT confer substrate selectivity, and how the exosome enforces heterochromatic silencing in concert with HP1 proteins and the Human Silencing Hub (HUSH) complex and preserves three-dimensional genome architecture at insulators and enhancers, such as the protocadherin locus where RNA surveillance, CTCF insulation, and heterochromatin converge. We then examine the consequences of failure: exosomopathies such as pontocerebellar hypoplasia, loss of DIS3- and PAXT-mediated tumor suppression in cancer, and age-related erosion of surveillance that permits transposable element de-repression, RIG-1/MDA5 and cGAS-STING-driven inflammation, cellular senescence, and neurodegeneration. We conclude that the exosome couples RNA decay to epigenetic state across the lifespan, positioning RNA surveillance as an emerging therapeutic target. Full article

Plant-derived exosome-like nanoparticles (PELNs) are lipid bilayer nanostructures containing endogenous lipids, proteins, nucleic acids, and phytochemicals, which have attracted increasing interest as bioinspired carriers for cancer therapy. This review evaluates how plant source, isolation, purification procedures, vesicle composition, cargo-loading strategy, and administration route shape the quality and tumor-delivery performance of PELNs. The available evidence indicates that plant source and processing are major determinants of particle size, purity, surface charge, cargo profile, and biological activity. Ultracentrifugation remains widely used but is limited by contaminant co-isolation and poor scalability, whereas density-gradient purification and size-exclusion chromatography improve purity, and ultrafiltration and tangential flow filtration offer greater potential for large-scale manufacturing. Passive incubation generally preserves vesicle integrity and is most suitable for hydrophobic small molecules, whereas electroporation, sonication, and extrusion can increase cargo loading but may cause aggregation, membrane remodeling, or loss of endogenous components. Preclinical studies suggest that PELNs can exert intrinsic antitumor effects, modulate the tumor microenvironment, improve chemotherapeutic delivery, and help overcome drug resistance. However, evidence for in vivo tumor-targeting remains less robust than evidence for cellular uptake, and direct comparisons with established nanocarriers remain scarce. Clinical translation will require standardized nomenclature and characterization, reproducible manufacturing, quantitative loading and release assays, route-specific biodistribution studies, and repeated-dose safety evaluation. These findings provide a framework for the rational development of PELNs as reproducible tumor-oriented nanocarriers. Full article

Liquid biopsy has emerged as a transformative approach in modern oncology, offering minimally invasive access to tumor-derived biomarkers through the analysis of circulating tumor DNA, cell-free DNA, and extracellular vesicles such as exosomes. Unlike conventional tissue biopsies, liquid biopsy enables real-time monitoring of tumor dynamics, molecular heterogeneity, treatment response, and the development of therapeutic resistance. Recent advances in ultra-sensitive molecular technologies, including digital droplet polymerase chain reaction, next-generation sequencing, methylation profiling, and fragmentomic analysis, have substantially improved the sensitivity and specificity of circulating nucleic acid detection, facilitating their integration into precision cancer medicine. ctDNA analysis has demonstrated significant clinical utility across multiple malignancies, including lung, breast, colorectal, pancreatic, and prostate cancers, particularly in the identification of actionable genomic alterations, minimal residual disease, and mechanisms of acquired resistance. In parallel, cell-free DNA provides broader insights into tumor biology and systemic genomic alterations, while exosomes contribute additional layers of molecular information through the transport of nucleic acids, proteins, and signaling molecules involved in intercellular communication and tumor microenvironment modulation. The integration of artificial intelligence and machine learning approaches further enhances the interpretative power of liquid biopsy-derived datasets and supports the development of personalized therapeutic strategies. Despite these advances, important challenges remain, including low tumor fraction in early-stage disease, biological and technical variability, clonal hematopoiesis-associated false positives, assay standardization, and cost-effectiveness considerations. Nevertheless, the expanding clinical applicability of liquid biopsy technologies positions them as essential components of contemporary precision oncology. This review summarizes the biological foundations, analytical methodologies, current clinical applications, technological innovations, and future perspectives of circulating tumor DNA, cell-free DNA, and exosome-based liquid biopsies in cancer diagnosis, monitoring, and personalized treatment strategies. Full article

Extracellular vesicles (EVs), particularly small EVs or exosomes, are promising cell-free therapeutics with superior biocompatibility and intrinsic targeting for synthetic nanoparticles. However, conventional bulk preparation methods suffer from low yield, poor reproducibility, and structural instability. Microfluidic technologies resolve these issues by enabling precise, automated, and low-shear fluidic manipulation. This mini-review highlights recent advances in microfluidic-engineered exosomes for cancer immunotherapy and infectious diseases. We evaluate critical microfluidic strategies for isolation, surface engineering, and cargo loading, contrasting platforms like ExoArc, acoustofluidics, cellular nanoporation, and electroporation. Particular emphasis is placed on complex modalities, including immune cell-derived exosomes (IEX), neo-antigen presentation, chimeric antigen receptor (CAR)-derived exosomes, and targeted siRNA delivery networks. Crucially, we analyze the technological disconnect between analytical microfluidic scales and massive therapeutic manufacturing volumes, addressing how physical forces risk damaging conformationally sensitive surface proteins (e.g., CAR scFv). Finally, we outline future perspectives, including high-throughput 3D-multiplexed networks, stimulus-responsive scarless elution, and integrated “sample-to-therapy” circuits. Guided by the MISEV2023 guidelines, this review frames the path toward standardized, clinical-scale engineering of multi-functional, cell-free immunotherapies. Full article

Background/Objectives: Prostate cancer is the second most frequent cancer among men and the 5th leading cause of cancer death among men worldwide. Identification of urine-derived biomarkers, such as exosomal miRNAs, in liquid biopsies for prostate cancer could be very beneficial for screening and active surveillance. Methods: Urine was collected from 42 patients with biopsy-proven evidence of prostate cancer and exosomes were extracted. Transcriptomic analysis was performed on the urine-derived exosomal miRNA and compared to the urine-derived exosomal miRNA profiles from 10 normal control donors and 15 von Hippel-Lindau (VHL) syndrome patients with clear cell renal cell carcinoma (ccRCC). Results: Urine-derived exosomal miRNA profiles of prostate patients were significantly different from normal control individuals. Significantly increased expression of miR-122-5p and decreased expression of miR-125-5p and miR-16-5p were observed in the urine-derived exosomes from prostate cancer patients. Significant upregulation of miR-30a-5p and downregulation of miR-320-5p, miR-320b, and miR-320c were observed in the urine-derived exosomes from both prostate cancer patients and VHL patients with ccRCC, indicating these miRNAs could be non-specific markers of urological cancer. Increased expression of miR-10a-5p and miR-30e-5p or miR-532-5p and miR-206 correlated with the presence of either extracapsular or perineural invasion, respectively. Conclusions: This study highlights the potential for urine-derived exosomal miRNA profiles to identify the presence of prostate cancer and predict clinical features, additionally showing that miRNA signals could be non-specific markers of urologic cancer types. Further validation studies are necessary to demonstrate the utility of urine-derived exosomal miRNA profiles as biomarkers for diagnosis or prognosis in prostate cancer. Full article

Lung cancer remains the leading cause of cancer-related mortality worldwide in both males and females. Despite recent advances in precision-targeted therapeutics, mortality rates remain high, largely due to delayed diagnoses when curative interventions are no longer feasible. Recent studies from our group demonstrated that the LINE-1 mRNA and associated miRNA cargo of plasma exosomes can be used as sensitive and specific diagnostic and prognostic biomarkers of non-small-cell lung cancer (NSCLC). Because exosomes from various cancer types can be detected in urine, we extended our investigation to examine these analytes in urine exosomes from NSCLC patients. LINE-1 ORF1 and ORF2 mRNA levels, along with miR-21-5p, miR-126-3p, miR-210-3p, miR-221-3p, Let-7b-5p, miR-146a-5p, miR-222-3p, miR-9-5p, and miR-1277-5p, were higher in urine exosomes from NSCLC patients compared to healthy controls. The cargo of urine-derived exosomes often mirrored that of plasma exosomes and correlated with several clinicopathologic characteristics. The strong predictive performance of urine exosomal RNAs distinguishing NSCLC patients from controls suggests these measurements may serve as a complementary and readily accessible source for noninvasive assessment of patients with NSCLC. Full article

Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neuroinflammatory disorder often leading to demyelination of the spinal cord. Progression to HAM/TSP is closely associated with the high proviral load and the presence of virally infected CD4+ T cells that release extracellular vesicles (EVs). Exosomes, an EV subtype released by many cell types, transport proteins and nucleic acids that regulate intercellular communication and have been implicated in the progression of cancer and neuroinflammatory diseases. Herein, we have studied the effect of exosomes from HTLV-1 infected cells on the Peripheral Blood Mononuclear Cells (PBMCs) of HAM/TSP patients by single-cell sequencing utilizing innovative Honeycomb technology. We observed a distinct transcriptional response in monocyte populations compared with other immune cell types. Given that monocytes remain understudied in HTLV-1 pathogenesis, these findings highlight a potential role for infection-derived exosomes in shaping monocyte-driven immune dysregulation in HAM/TSP. A total of 41 genes were identified to be differentially expressed in HAM/TSP monocytes treated with exosomes; 28 were upregulated and 13 were downregulated. The most significantly altered genes are involved in chemokine activity and signaling, macrophage differentiation, lipid metabolism, and lysosomal function. Overall, our data suggests that exosome-treated HAM/TSP monocytes undergo immune remodeling that favors cell recruitment, activation, and a shift toward a mixed M1/M2-like phenotype. Such a shift may support viral persistence and chronic inflammation. These findings highlight a potential therapeutic pathway for addressing HTLV-1-induced neuroinflammation by modulating exosome-mediated signaling. Full article

Inflammatory bowel disease (IBD) represents a growing global health threat that markedly increases colorectal cancer risk, yet conventional immunosuppressive agents achieve mucosal healing in only a limited subset of patients. M2-polarized macrophages have been recognized as crucial regulators of mucosal repair through their ability to maintain intestinal microenvironment homeostasis. Here, we investigated the potential effects and mechanisms of macrophage-derived exosomes (Exos) on epithelial barrier function in a murine model of IBD. Murine colitis was induced by intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by treatment with Exos isolated from IL-33-treated macrophages (IL-33-Exos) or untreated macrophages (PBS-Exos). Our findings showed that IL-33-Exos markedly ameliorated inflammatory intestinal mucosal injury and improved intestinal barrier dysfunction. Concurrently, IL-33-Exos mitigated intestinal epithelial cell damage, thereby preserving intestinal mucosal integrity. Mechanistic studies revealed that the beneficial effects of IL-33-Exos were implicated in upregulation of Wnt/β-catenin signaling in intestinal epithelial cells. Translationally, these findings suggest that IL-33-Exos may promote epithelial repair in experimental colitis, offering a novel therapeutic avenue for clinical management of inflammatory bowel disease. Full article

Introduction: Cutaneous T cell lymphoma (CTCL), most commonly known as mycosis fungoides (MF), is characterized by an increasingly immunosuppressive tumor microenvironment (TME) as the disease progresses. Cancer-associated fibroblasts (CAFs) are key stromal components that support a permissive niche, in part through the secretion of small extracellular vesicles (sEVs), predominantly exosomes, that mediate intercellular communication. We investigated the immunomodulatory role of exosome-enriched sEVs derived from MF fibroblasts (MF-Fs) compared to normal fibroblasts (N-Fs). Materials and Methods: Primary MF-Fs from early-stage MF biopsies and N-Fs from healthy skin were cultured in vitro. sEVs enriched with exosomes were isolated by ultracentrifugation and characterized by flow cytometry (CD81), electron microscopy, Nanosight analysis, and protein quantification, and their uptake by normal peripheral blood mononuclear cells (nPBMCs) was confirmed using PKH26-labeled sEVs. nPBMCs, monocytes, CD4⁺ and CD8⁺ T cells from healthy donors were exposed to MF-F or N-F sEVs. Cell viability was assessed using MTT and trypan blue exclusion assays. Mass cytometry (CyTOF) profiled immune subsets and regulatory proteins for preliminary observation. Monocyte polarization was evaluated by flow cytometry for M1 (CD80, CD86) and M2 (CD163, CD206) markers and PD-L1 expression; M1/M2-associated cytokines and sEV-microRNAs were quantified by qRT-PCR. Results: Both MF-F and N-F sEVs were internalized by nPBMCs and reduced their viability, with a more pronounced effect observed for MF-F sEVs. In nPBMCs, MF-F sEVs also increased the frequency of M2-like macrophages, decreased M1 polarization, and enhanced PD-L1 expression. In primary monocytes, MF-F- compared with N-F-derived sEVs upregulated M2-associated cytokines (IL-10, TGF-β), increased PD-L1 expression, and generated M2-like cells that suppressed CD4⁺ and CD8⁺ T cell viability. Conclusions: MF-F sEVs promote an immunosuppressive TME and represent potential therapeutic or biomarker targets in MF. Full article

For decades, peritoneal metastases (PM) have been regarded as a terminal manifestation of advanced malignancies and managed primarily with palliative intent because of limited sensitivity to systemic therapies. Accumulating clinical, molecular, and immunological evidence now supports the view that PM is not merely an anatomic pattern of spread but a distinct metastatic niche with characteristic biological, microenvironmental, and therapeutic features. This review summarizes the major routes of PM development—transcoelomic, lymphatic, and hematologic dissemination—and emphasizes how these pathways converge through shared biological programs. Core mechanisms include epithelial–mesenchymal transition (EMT), adhesion signaling, extracellular matrix remodeling, and tumor–immune cell interactions. A central focus is the peritoneal tumor microenvironment: mesothelial-to-mesenchymal transition, cancer-associated fibroblast activity, adipocyte-derived metabolic support, macrophage polarization, and regulatory T-cell enrichment collectively shape an immunotolerant and treatment-resistant niche on the peritoneal surface. In addition, evidence from pre-metastatic niche biology suggests that primary tumor-derived exosomes and epitranscriptomic regulation can prime the peritoneal environment before overt implantation. These features provide a biological rationale for locoregional strategies such as cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, as well as emerging intraperitoneal modalities and microenvironment-targeted approaches. Finally, organoid platforms, liquid biopsy-based minimal residual disease monitoring, and theranostic technologies may enable more personalized, biology-driven management of PM. Full article

To characterize the distinct expression profiles of microRNAs (miRNAs) in serum and tissue and to delineate the heterogeneity of their regulatory mechanisms in early-stage ovarian cancer (EOC), thereby identifying candidate biomarkers for non-invasive early diagnosis. Differentially expressed miRNAs were identified by integrating publicly available datasets of EOC tissues and serum samples from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Core miRNAs were subsequently screened through integrated differential expression analysis, weighted gene co-expression network analysis (WGCNA), and feature importance ranking derived from optimized machine learning models. Protein–protein interaction (PPI) networks and functional enrichment analyses (GO and KEGG) were performed on predicted target genes to systematically compare the functional discrepancies between serum- and tissue-derived miRNAs. No overlapping core miRNAs were observed between the two compartments. Serum miRNAs exhibited an overall up-regulated trend, whereas tissue miRNAs were predominantly down-regulated. Although the regulatory pathways demonstrated significant heterogeneity, they ultimately converged on the cell cycle and the PI3K-Akt signaling pathway, indicating high functional homology. Furthermore, serum miRNAs are not merely passive leakage products from tissues; current evidence suggests they may be selectively packaged into exosomes to participate in tumor regulation. Despite divergent expression profiles, serum and tissue miRNAs share homologous regulatory functions in EOC. These findings suggest that serum miRNAs accurately reflect the core molecular status of tumor tissues, providing a robust molecular foundation for liquid biopsy-based early detection strategies. Full article

The study aimed to investigate the individual therapeutic effects of melatonin and umbilical cord-derived mesenchymal stem cell exosomes (UC-MSC-Exo) separately on BE(2)-C neuroblastoma cells. Melatonin is recognized for its anti-cancer, antioxidant, and apoptosis-inducing properties, and its ability to cross the blood–brain barrier. UC-MSC-Exos are nanovesicles from mesenchymal stem cells that can also cross the blood–brain barrier and transport biologically active molecules. The potential therapeutic benefits of each independent agent in treating BE(2)-C neuroblastoma cells were investigated. Melatonin and UC-MSC-Exos were examined on BE(2)-C neuroblastoma cells at varying concentrations and time intervals to evaluate cell viability and apoptosis. Both melatonin and UC-MSC-Exo independently reduced cell viability and induced apoptosis in a manner that depended on the dosage and duration of exposure. Melatonin had an IC₅₀ of 2.68 mM after 24 h, while UC-MSC-Exo showed an IC₅₀ of 25.3 μg/mL after 48 h, with no cytotoxic effects observed at 24 h. Specifically, individual concentrations of 2.5 mM and 5 mM of melatonin, as well as 50 µg/mL and 100 µg/mL of UC-MSC-Exo, led to significant levels of apoptotic and necrotic cells at 48 and 72 h (p < 0.001). Our findings suggest that the individual administration of melatonin and UC-MSC-Exo may hold therapeutic potential for neuroblastoma cells, particularly given their ability to cross the blood–brain barrier. Further in vivo research is required to evaluate their clinical utility. Full article

Hepatocellular carcinoma (HCC) remains a major global health burden, characterized by late diagnosis, limited therapeutic options, and high mortality rates. Conventional diagnostic tools such as serum α-fetoprotein testing and imaging lack sufficient sensitivity for early detection. In recent years, liquid biopsy has emerged as a minimally invasive approach that enables real-time molecular profiling of tumors through the analysis of circulating biomarkers such as nucleic acids, proteins, and extracellular vesicles. Recent advances have underscored exosomes—nano-sized extracellular vesicles (EVs) secreted by nearly all cell types—as pivotal mediators of intercellular communication and dynamic carriers of tumor-derived molecular information, offering exciting prospects for early cancer detection and personalized therapy. In HCC, EV microRNAs (miRNAs) participate in multiple oncogenic processes, including proliferation, angiogenesis, epithelial–mesenchymal transition, and immune modulation. Specific EV-associated miRNAs, such as miR-21, miR-122, miR-224, and miR-221, show distinctive expression profiles in HCC and correlate with tumor stage, metastasis, and patient prognosis. Moreover, panels of circulating EV-associated miRNAs demonstrate superior diagnostic accuracy compared with traditional biomarkers, underscoring their potential as non-invasive tools for early detection and disease monitoring. Their inherent stability in biofluids and resistance to enzymatic degradation further support their application in liquid biopsy approaches. Despite promising results, continued research is essential to validate EV-associated miRNA signatures and to integrate these “silent messengers” into routine clinical practice for precision management of hepatocellular carcinoma. Full article