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Published on: December 9, 2016
Establishment and characterization of a patient-derived metastatic extraskeletal Ewing sarcoma cell line ES-ZSS-1
Chenlu Zhang1, Mengling Liu1, Lijuan Luan2
1Department of Medical Oncology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, China.
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.
Insights
Researchers developed a new patient-derived cell line model for metastatic Ewing sarcoma (ES). This model accurately reflects patient tumors, offering a valuable tool for discovering novel therapies for this challenging cancer.
Area of Science:
- Oncology
- Cancer Biology
- Genetics
Background:
- Metastatic Ewing sarcoma (ES) treatment options are limited.
- Developing effective therapies is hindered by the lack of relevant preclinical models.
- Innovative therapeutic strategies are crucial for improving patient outcomes.
Purpose of the Study:
- To establish and characterize a novel patient-derived xenograft (PDX) cell line model for metastatic extraskeletal Ewing sarcoma.
- To create a reliable preclinical tool for drug discovery and research in metastatic ES.
Main Methods:
- A patient-derived xenograft (PDX) cell line, ES-ZSS-1, was established from metastatic extraskeletal ES tumor tissue.
- The cell line was characterized for morphological, histopathological, and genetic features, including gene expression profiling.
- In vitro passages were performed to assess cell line stability and behavior.
Main Results:
- The ES-ZSS-1 cell line recapitulated the original patient tumor's phenotype and genotype.
- The characteristic EWSR1-FLI1 fusion was present.
- Frequent STAG2 mutations, increased Twist1 expression, and evidence of epithelial-to-mesenchymal transition (EMT) were identified, potentially linked to metastasis and chemoresistance.
Conclusions:
- The novel ES-ZSS-1 cell line serves as a robust and clinically relevant model for metastatic Ewing sarcoma.
- This PDX model provides a valuable platform for investigating the mechanisms of ES metastasis and chemoresistance.
- It facilitates the development and testing of new therapeutic approaches for metastatic ES.
