American Association for Cancer Research
Browse
ccr-23-1111_supplemental_table_3_suppst3.xlsx (9.82 MB)

Supplemental Table 3 from Cancer-Associated Fibroblast-Like Tumor Cells Remodel the Ewing Sarcoma Tumor Microenvironment

Download (9.82 MB)
dataset
posted on 2023-12-15, 08:41 authored by Emma D. Wrenn, April A. Apfelbaum, Erin R. Rudzinski, Xuemei Deng, Wei Jiang, Sudha Sud, Raelene A. Van Noord, Erika A. Newman, Nicolas M. Garcia, Aya Miyaki, Virginia J. Hoglund, Shruti S. Bhise, Sami B. Kanaan, Olivia G. Waltner, Scott N. Furlan, Elizabeth R. Lawlor

Supplemental Table 3. RNAseq-derived gene expression data for CD73- and CD73+ A673 and CHLA10 cells.

Funding

National Cancer Institute (NCI)

United States Department of Health and Human Services

Find out more...

American Association for Cancer Research/QuadW Foundation

Sam Day Foundation

1M4 Anna

Lafontaine U-Can-Cer-Vive Foundation

History

ARTICLE ABSTRACT

Despite 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. Single-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. We 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. EwS 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

Usage metrics

    Clinical Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC