Department of Medical Oncology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, China.
Department of Pathology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, China.
Hum Cell. 2024 Oct 30;38(1):12. doi: 10.1007/s13577-024-01133-3.
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.
治疗转移性尤文肉瘤（Ewing sarcoma，ES）的方法并不完善；因此，需要开发创新的治疗方法。然而，缺乏临床相关的 ES 模型阻碍了该疾病药物的发现。在本研究中，我们建立并鉴定了一个患者来源的异种移植（patient-derived xenograft，PDX）细胞系模型，该模型使用一名转移性骨外 ES 患者的肿瘤组织构建。发现这些细胞再现了患者肿瘤的形态学和组织病理学特征，并被命名为 ES-ZSS-1。这些细胞携带特征性的 EWSR1-FLI1 融合，并在体外连续传代。通过进行基因表达谱分析，我们发现 STAG2 突变最为常见。记录到 Twist1 和上皮间质转化（epithelial-to-mesenchymal transition，EMT）的增加。这些遗传特征可能与转移和化疗耐药性有关。总之，我们开发的新型患者来源的 ES 细胞系在表型和基因型上非常类似于患者肿瘤，使其成为研究转移性 ES 的可靠工具。
