Establishment and characterization of a patient-derived metastatic extraskeletal Ewing sarcoma cell line ES-ZSS-1

Hum Cell. 2024 Oct 30;38(1):12. doi: 10.1007/s13577-024-01133-3.

Abstract

The methods available for treating metastatic Ewing sarcoma (ES) are inadequate; thus, innovative therapeutic approaches need to be developed. However, the lack of clinically relevant ES models has hindered the discovery of drugs for this disease. In this study, we established and characterized a patient-derived xenograft (PDX) cell line model, which was constructed using tumor tissue from a patient with metastatic extraskeletal ES. The cells were found to recapitulate the morphological and histopathological features of the patient tumor and were designated as ES-ZSS-1. The cells harbor the characteristic EWSR1-FLI1 infusion and underwent successive passages in vitro. By performing gene expression profiling, we found that the mutation in STAG2 was the most frequent. An increase in Twist1 and epithelial-to-mesenchymal transition (EMT) was recorded. These genetic features might be relevant to metastasis and resistance to chemotherapy. To summarize, the novel patient-derived ES cell line we developed closely mimics the phenotype and genotype of patient tumors, making it a reliable tool for research on metastatic ES.

Keywords: Epithelial-to-mesenchymal transition; Extraskeletal Ewing sarcoma; Genomic characteristic; Metastatic and drug resistance; Patient-derived cancer cell line.

MeSH terms

  • Animals
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology
  • Bone Neoplasms / secondary
  • Cell Line, Tumor
  • Cohesins
  • Epithelial-Mesenchymal Transition* / genetics
  • Heterografts
  • Humans
  • Mutation
  • Neoplasm Metastasis / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Oncogene Proteins, Fusion / genetics
  • Proto-Oncogene Protein c-fli-1 / genetics
  • RNA-Binding Protein EWS / genetics
  • Sarcoma, Ewing* / genetics
  • Sarcoma, Ewing* / pathology
  • Twist-Related Protein 1 / genetics

Substances

  • STAG2 protein, human
  • Twist-Related Protein 1
  • TWIST1 protein, human
  • RNA-Binding Protein EWS
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Protein c-fli-1
  • EWSR1-FLI1 fusion protein, human
  • Cohesins