CD99 Modulates the Proteomic Landscape of Ewing Sarcoma Cells and Related Extracellular Vesicles

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,...

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Published in:International journal of molecular sciences 2024-02, Vol.25 (3), p.1588
Main Authors: De Feo, Alessandra, Manfredi, Marcello, Mancarella, Caterina, Maqueda, Joaquín J, De Giorgis, Veronica, Pignochino, Ymera, Sciandra, Marika, Cristalli, Camilla, Donadelli, Massimo, Scotlandi, Katia
Format: Article
Language:English
Subjects:
12E7 Antigen - metabolism
Annotations
Antigens
biomarkers
Bone Neoplasms - metabolism
Cell differentiation
Cell Line, Tumor
Cell Movement - genetics
Cells
Child
Epigenetic inheritance
Epigenetics
Ewing sarcoma
Ewings sarcoma
Extracellular vesicles
Extracellular Vesicles - metabolism
Gene Expression Regulation, Neoplastic
heterogeneity
Humans
Mass spectrometry
Metastasis
MicroRNAs
Neomycin
Oncogene Proteins, Fusion - genetics
Proteins
proteomic
Proteomics
Sarcoma
Sarcoma, Ewing - pathology
Scientific equipment and supplies industry
Scientific imaging
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms25031588