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 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 versus SSEA-4 expression was not related to expression levels of the EWSR1-FLI1 fusion transcript or markers of epithelial/mesenchymal plasticity. SSEA-4 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.
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http://dx.doi.org/10.1038/s41598-024-62849-8 | DOI Listing |
Vavilovskii Zhurnal Genet Selektsii
November 2024
Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
Frontotemporal dementia with parkinsonism-17 is a neurodegenerative disease characterised by pathological aggregation of the tau protein with the formation of neurofibrillary tangles and subsequent neuronal death. The inherited form of frontotemporal dementia can be caused by mutations in several genes, including the MAPT gene on chromosome 17, which encodes the tau protein. As there are currently no medically approved treatments for frontotemporal dementia, there is an urgent need for research using in vitro cell models to understand the molecular genetic mechanisms that lead to the development of the disease, to identify targets for therapeutic intervention and to test potential drugs to prevent neuronal death.
View Article and Find Full Text PDFPoult Sci
December 2024
Department of Reproductive Biotechnology and Cryoconservation, National Research Institute of Animal Production, Balice 32-083, Poland. Electronic address:
The nervous system's regenerative potential has sparked interest in exploring novel approaches to generate Schwann cell-like cells (SC-LCs) from chicken blastoderm (B)-derived embryonic stem cells (B-ESCs). This study investigates the hypothesis that specific growth factors, when used during ex-ovo culture, can induce the differentiation of chicken B-ESCs into cells resembling Schwann cells (SCs). Blastodermal cells (BCs) were isolated from in vivo-fertilized eggs at stage X followed by 14-d proliferative culture (PRC) of B-ESCs and subsequent 14-d glial/neurolemmogenic differentiation culture (DFC).
View Article and Find Full Text PDFGlycoconj J
December 2024
Department of Urology, University of the Ryukyus Graduate School of Medicine, 207 Uehara, Nishihara, Nakagami-gun, Okinawa, 903-0215, Japan.
Stage-specific embryonic antigen-4 (SSEA-4) is a developmentally regulated antigen, while expression level of SSEA-4 and / or its synthase ST3GAL2 is associated with prognosis in various malignancies. We have reported a prominent increase of SSEA-4 in castration-resistant prostate cancer (CRPC) and its negative correlation with the androgen receptor (AR). Meanwhile, loss of AR has increased to approximately 30% with the growing use of androgen receptor signaling inhibitor for metastatic CRPC (mCRPC).
View Article and Find Full Text PDFSci Rep
May 2024
Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer Campus 1, 38149, Muenster, Germany.
Heliyon
April 2024
Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.
Myocardial infarction (MI) is a leading cause of death worldwide, resulting in extensive loss of cardiomyocytes and subsequent heart failure. Inducing cardiac differentiation of stem cells is a potential approach for myocardial regeneration therapy to improve post-MI prognosis. Mesenchymal stem cells (MSCs) have several advantages, including immune privilege and multipotent differentiation potential.
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