Back to Search
Start Over
Ganglioside SSEA-4 in Ewing sarcoma marks a tumor cell population with aggressive features and is a potential cell-surface immune target.
- Source :
-
Scientific reports [Sci Rep] 2024 May 24; Vol. 14 (1), pp. 11935. Date of Electronic Publication: 2024 May 24. - Publication Year :
- 2024
-
Abstract
- Carbohydrate markers of immature cells during prenatal human development can be aberrantly expressed in cancers and deserve evaluation as immune targets. A candidate target in Ewing sarcoma is the globo-series ganglioside stage-specific embryonic antigen-4 (SSEA-4). We detected SSEA-4 expression on the cell surface of all of 14 EwS cell lines and in 21 of 31 (68%) primary EwS tumor biopsies. Among paired subpopulations of tumor cells with low versus high SSEA-4 expression, SSEA-4 <superscript>high</superscript> expression was significantly and consistently associated with functional characteristics of tumor aggressiveness, including higher cell proliferation, colony formation, chemoresistance and propensity to migrate. SSEA-4 <superscript>low</superscript> versus SSEA-4 <superscript>high</superscript> expression was not related to expression levels of the EWSR1-FLI1 fusion transcript or markers of epithelial/mesenchymal plasticity. SSEA-4 <superscript>low</superscript> cells selected from bulk populations regained higher SSEA-4 expression in vitro and during in vivo tumor growth in a murine xenograft model. T cells engineered to express SSEA-4-specific chimeric antigen receptors (CARs) specifically interacted with SSEA-4 positive EwS cells and exerted effective antigen-specific tumor cell lysis in vitro. In conclusion, with its stable expression and functional significance in EwS, SSEA-4 is an attractive therapeutic immune target in this cancer that deserves further evaluation for clinical translation.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Female
Humans
Mice
Biomarkers, Tumor metabolism
Biomarkers, Tumor genetics
Bone Neoplasms immunology
Bone Neoplasms pathology
Bone Neoplasms genetics
Bone Neoplasms metabolism
Cell Line, Tumor
Cell Proliferation
Gangliosides
Glycosphingolipids
Xenograft Model Antitumor Assays
Sarcoma, Ewing pathology
Sarcoma, Ewing metabolism
Sarcoma, Ewing genetics
Stage-Specific Embryonic Antigens metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 38789477
- Full Text :
- https://doi.org/10.1038/s41598-024-62849-8