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Ganglioside SSEA-4 in Ewing sarcoma marks a tumor cell population with aggressive features and is a potential cell-surface immune target.
Jamitzky, Silke; Altvater, Bianca; Krekeler, Carolin; Hoen, Laura; Brandes, Caroline; Ebbinghaus, Julia; Richter, Lisa; Kosel, Lisa; Ochs, Laurin; Farwick, Nicole; Urban, Katja; Kluge, Lena; Bücker, Lara; Görlich, Dennis; Johnston, Ian C D; Pfeifer, Rita; Hartmann, Wolfgang; Rossig, Claudia; Kailayangiri, Sareetha.
Affiliation
  • Jamitzky S; Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer Campus 1, 38149, Muenster, Germany.
  • Altvater B; Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer Campus 1, 38149, Muenster, Germany.
  • Krekeler C; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands.
  • Hoen L; Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer Campus 1, 38149, Muenster, Germany.
  • Brandes C; Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer Campus 1, 38149, Muenster, Germany.
  • Ebbinghaus J; Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer Campus 1, 38149, Muenster, Germany.
  • Richter L; Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer Campus 1, 38149, Muenster, Germany.
  • Kosel L; Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer Campus 1, 38149, Muenster, Germany.
  • Ochs L; Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer Campus 1, 38149, Muenster, Germany.
  • Farwick N; Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer Campus 1, 38149, Muenster, Germany.
  • Urban K; Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer Campus 1, 38149, Muenster, Germany.
  • Kluge L; Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer Campus 1, 38149, Muenster, Germany.
  • Bücker L; Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer Campus 1, 38149, Muenster, Germany.
  • Görlich D; Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer Campus 1, 38149, Muenster, Germany.
  • Johnston ICD; Institute of Biostatistics and Clinical Research, University of Muenster, Schmeddingstr. 56, 48149, Muenster, Germany.
  • Pfeifer R; Miltenyi Biotec B.V. & Co. KG, Friedrich-Ebert-Straße 68, 51429, Bergisch Gladbach, Germany.
  • Hartmann W; Miltenyi Biotec B.V. & Co. KG, Friedrich-Ebert-Straße 68, 51429, Bergisch Gladbach, Germany.
  • Rossig C; Gerhard-Domagk-Institute of Pathology, University of Muenster, Domagkstr. 17, 48149, Muenster, Germany.
  • Kailayangiri S; Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer Campus 1, 38149, Muenster, Germany. rossig@ukmuenster.de.
Sci Rep ; 14(1): 11935, 2024 05 24.
Article in En | MEDLINE | ID: mdl-38789477
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-4high expression was significantly and consistently associated with functional characteristics of tumor aggressiveness, including higher cell proliferation, colony formation, chemoresistance and propensity to migrate. SSEA-4low versus SSEA-4high expression was not related to expression levels of the EWSR1-FLI1 fusion transcript or markers of epithelial/mesenchymal plasticity. SSEA-4low 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.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Sarcoma, Ewing / Stage-Specific Embryonic Antigens Limits: Animals / Female / Humans Language: En Journal: Sci Rep Year: 2024 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Sarcoma, Ewing / Stage-Specific Embryonic Antigens Limits: Animals / Female / Humans Language: En Journal: Sci Rep Year: 2024 Document type: Article Affiliation country: Country of publication: