ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Cancer-Associated Fibroblast-Like Tumor Cells Remodel the Ewing Sarcoma Tumor Microenvironment.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 31 citations in OpenAlex.
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- Pediatric sarcomas: challenges and opportunities.Genes & development · 2026Review
- Fusion-driven oncogenic programs shape the immune landscape in translocation renal cell carcinoma.Nature communications · 2026Article
- The Single-Cell Pediatric Cancer Atlas: Data portal and open-source tools for single-cell transcriptomics of pediatric tumors.Cell genomics · 2026Article
- Single-cell transcriptomics reveals glycolytic heterogeneity and identifies STC2 as a key regulator of metabolic reprogramming in osteosarcoma.Molecular and cellular biochemistry · 2026Article
- Emerging Roles of Adenosine Metabolism in Astrocytes During Brain Injury.CNS neuroscience & therapeutics · 2026Review
- A Pan-Cancer Ex Vivo Drug Screen Atlas for Functional Precision Oncology.bioRxiv : the preprint server for biology · 2026Article
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- Autocrine TGFβ2 enforces a transcriptionally hybrid cell state in Ewing sarcoma.Science advances · 2026Article
- Spatial Profiling Identifies Tumor-Associated Stroma Enrichment and MIF as Potential Immunotherapy Targets in Primary Ewing Sarcomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Review
- Pathology-interpretable radiomic model for predicting clinical outcome in patients with osteosarcoma: a retrospective, multicenter study.BMC medicine · 2025Article
- Cancer‑associated fibroblasts in human malignancies, with a particular emphasis on sarcomas (Review).International journal of oncology · 2025Review
- New Approaches to Investigate Novel Agents in Ewing Sarcoma: A Report From the Children's Oncology Group Bone Tumor Committee.Pediatric blood & cancer · 2025Review
- Article
- Review
- TGFβ Inhibition during Radiotherapy Enhances Immune Cell Infiltration and Decreases Metastases in Ewing Sarcoma.Cancer research communications · 2025Article
- Cancer-Associated Fibroblasts: Heterogeneity, Cancer Pathogenesis, and Therapeutic Targets.MedComm · 2025Review
- Autocrine TGFβ2 enforces a transcriptionally hybrid cell state in Ewing sarcoma.bioRxiv : the preprint server for biology · 2025Article
- Advances in spatial transcriptomics and its application in the musculoskeletal system.Bone research · 2025Review
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
purposeDespite limited genetic and histologic heterogeneity, Ewing sarcoma (EwS) tumor cells are transcriptionally heterogeneous and display varying degrees of mesenchymal lineage specification in vitro. In this study, we investigated if and how transcriptional heterogeneity of EwS cells contributes to heterogeneity of tumor phenotypes in vivo. EXPERIMENTAL
designSingle-cell proteogenomic-sequencing of EwS cell lines was performed and integrated with patient tumor transcriptomic data. Cell subpopulations were isolated by FACS for assessment of gene expression and phenotype. Digital spatial profiling and human whole transcriptome analysis interrogated transcriptomic heterogeneity in EwS xenografts. Tumor cell subpopulations and matrix protein deposition were evaluated in xenografts and patient tumors using multiplex immunofluorescence staining.
resultsWe identified CD73 as a biomarker of highly mesenchymal EwS cell subpopulations in tumor models and patient biopsies. CD73+ tumor cells displayed distinct transcriptional and phenotypic properties, including selective upregulation of genes that are repressed by EWS::FLI1, and increased migratory potential. CD73+ cells were distinguished in vitro and in vivo by increased expression of matrisomal genes and abundant deposition of extracellular matrix (ECM) proteins. In epithelial-derived malignancies, ECM is largely deposited by cancer-associated fibroblasts (CAF), and we thus labeled CD73+ EwS cells, CAF-like tumor cells. Marked heterogeneity of CD73+ EwS cell frequency and distribution was detected in tumors in situ, and CAF-like tumor cells and associated ECM were observed in peri-necrotic regions and invasive foci.
conclusionsEwS tumor cells can adopt CAF-like properties, and these distinct cell subpopulations contribute to tumor heterogeneity by remodeling the tumor microenvironment. See related commentary by Kuo and Amatruda, p. 5002.
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