دورية أكاديمية
Cancer-Associated Fibroblast-Like Tumor Cells Remodel the Ewing Sarcoma Tumor Microenvironment.
| العنوان: | Cancer-Associated Fibroblast-Like Tumor Cells Remodel the Ewing Sarcoma Tumor Microenvironment. |
|---|---|
| المؤلفون: | Wrenn ED; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington., Apfelbaum AA; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington.; Cancer Biology PhD Program, University of Michigan, Ann Arbor, Michigan., Rudzinski ER; Pathology Department, Seattle Children's Hospital, Seattle, Washington., Deng X; Pathology Department, Seattle Children's Hospital, Seattle, Washington., Jiang W; Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan., Sud S; Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan., Van Noord RA; Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan., Newman EA; Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan., Garcia NM; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington., Miyaki A; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington., Hoglund VJ; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington., Bhise SS; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington., Kanaan SB; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington., Waltner OG; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington., Furlan SN; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington.; Department of Pediatrics, University of Washington, Seattle, Washington., Lawlor ER; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington.; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington.; Department of Pediatrics, University of Washington, Seattle, Washington. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Dec 15; Vol. 29 (24), pp. 5140-5154. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مواضيع طبية MeSH: | Sarcoma, Ewing*/pathology , Cancer-Associated Fibroblasts*/metabolism, Humans ; Tumor Microenvironment/genetics ; Cell Line, Tumor ; RNA-Binding Protein EWS/genetics ; RNA-Binding Protein EWS/metabolism ; Gene Expression Profiling ; Oncogene Proteins, Fusion/genetics ; Proto-Oncogene Protein c-fli-1/genetics ; Gene Expression Regulation, Neoplastic |
| مستخلص: | Purpose: 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. Experimental Design: 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. Results: 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. Conclusions: 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. (©2023 American Association for Cancer Research.) |
| التعليقات: | Update of: bioRxiv. 2023 Apr 13:2023.04.12.536619. doi: 10.1101/2023.04.12.536619. (PMID: 37090655) Comment in: Clin Cancer Res. 2023 Dec 15;29(24):5002-5004. doi: 10.1158/1078-0432.CCR-23-2259. (PMID: 37796143) |
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| معلومات مُعتمدة: | F31 CA247104 United States CA NCI NIH HHS; L40 CA264534 United States CA NCI NIH HHS; P30 CA015704 United States CA NCI NIH HHS; R01 CA215981 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (RNA-Binding Protein EWS) 0 (Oncogene Proteins, Fusion) 0 (Proto-Oncogene Protein c-fli-1) |
| تواريخ الأحداث: | Date Created: 20230720 Date Completed: 20231216 Latest Revision: 20240616 |
| رمز التحديث: | 20240616 |
| مُعرف محوري في PubMed: | PMC10801911 |
| DOI: | 10.1158/1078-0432.CCR-23-1111 |
| PMID: | 37471463 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
|---|---|
| DOI: | 10.1158/1078-0432.CCR-23-1111 |