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Ewing sarcoma (EWS) is an aggressive pediatric bone tumor characterized by unmet clinical needs and an incompletely understood epigenetic heterogeneity. Here, we considered CD99, a major surface molecule hallmark of EWS malignancy. Fluctuations in CD99 expression strongly impair cell dissemination, differentiation, and death. CD99 is also loaded within extracellular vesicles (EVs), and the delivery of CD99-positive or CD99-negative EVs dynamically exerts oncogenic or oncosuppressive functions to recipient cells, respectively. We undertook mass spectrometry and functional annotation analysis to investigate the consequences of CD99 silencing on the proteomic landscape of EWS cells and related EVs. Our data demonstrate that (i) the decrease in CD99 leads to major changes in the proteomic profile of EWS cells and EVs; (ii) intracellular and extracellular compartments display two distinct signatures of differentially expressed proteins; (iii) proteomic changes converge to the modulation of cell migration and immune-modulation biological processes; and (iv) CD99-silenced cells and related EVs are characterized by a migration-suppressive, pro-immunostimulatory proteomic profile. Overall, our data provide a novel source of CD99-associated protein biomarkers to be considered for further validation as mediators of EWS malignancy and as EWS disease liquid biopsy markers.
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http://dx.doi.org/10.3390/ijms25031588 | DOI Listing |
Expert Opin Drug Deliv
September 2025
Department of Hematology, The First Affiliated Hospital of Ningbo University, Ningbo, PR China.
Introduction: Hematopoietic stem cell transplantation (HSCT) is a promising treatment option for hematological malignancies. Despite its curative potential, it faces clinical challenges, including relapse and graft-versus-host disease (GVHD). Systemic toxicity due to chemotherapy is a significant problem in patients with hematological malignancies.
View Article and Find Full Text PDFBioimpacts
August 2025
Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, Russia.
Introduction: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS). CD4 CD25 Tregs, which normally suppress immune responses, exhibit impaired function in MS. Treg-derived extracellular vesicles (EVs) carry immunoregulatory proteins and miRNAs that modulate T-cell activity.
View Article and Find Full Text PDFCancer Lett
September 2025
Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China. Electronic address:
Dendritic cells (DCs) are the most powerful antigen-presenting cells (APCs) within the tumour microenvironment (TME), where they orchestrate T cell-mediated anti-tumour immunity and can also be reprogrammed to promote the progression of tumours in the TME. Extracellular vesicles (EVs) are very small and they are secreted by cells and wrapped in lipid bilayers that shuttle bioactive cargoes, including proteins, nucleic acids, and metabolites, to recipient cells, thereby influencing the progression of diseases, including cancer. DC-derived EVs (DC-EVs) play pivotal roles in the TME by mediating crosstalk with other immune and stromal cells to modulate inflammatory responses, angiogenesis, cell death, and immune evasion, thereby regulating the development and progression of tumours.
View Article and Find Full Text PDFAm J Physiol Lung Cell Mol Physiol
September 2025
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
Cystic Fibrosis (CF) is a multiorgan disease caused by mutations in the gene, leading to chronic pulmonary infections and hyperinflammation. Among pathogens colonizing the CF lung, is predominant, infecting over 50% of adults with CF, and becoming antibiotic-resistant over time. Current therapies for CF, while providing tremendous benefits, fail to eliminate persistent bacterial infections, chronic inflammation, and irreversible lung damage, necessitating novel therapeutic strategies.
View Article and Find Full Text PDFIEEE Trans Nanobioscience
September 2025
Extracellular vesicles (EVs) produced by stem cells are nanoscale carriers of bioactive compounds with regenerative and immunomodulatory capabilities similar to those of their parent cells. Their therapeutic potential outperforms traditional stem cell therapies by lowering hazards such tumorigenicity and allowing for precise delivery. To provide a high-efficiency platform for selectively isolating stem cell EVs from minimal serum quantities while overcoming the constraints of traditional approaches such as ultracentrifugation, we developed an immunoaffinity-based capture system utilizing SiO₂ wafers functionalized with gold nanoparticles (GNPs), polyethylene glycol (HS-PEG-COOH), and stem cell-specific antibodies.
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