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) |
References: | Nat Cell Biol. 2023 Feb;25(2):285-297. (PMID: 36658220) Signal Transduct Target Ther. 2020 Aug 25;5(1):166. (PMID: 32843638) Cancer Discov. 2015 Aug;5(8):806-20. (PMID: 26193902) Cell. 2017 Feb 9;168(4):613-628. (PMID: 28187284) J Clin Med. 2021 Apr 14;10(8):. (PMID: 33919988) Pediatr Pathol. 1994 Jan-Feb;14(1):111-25. (PMID: 8159609) N Engl J Med. 2021 Jan 14;384(2):154-164. (PMID: 33497548) PLoS One. 2009;4(4):e5415. (PMID: 19404404) Int J Cancer. 2020 Feb 15;146(4):895-905. (PMID: 30734283) Cancer Cell. 2021 Jun 14;39(6):810-826.e9. (PMID: 33930311) Cancer Res. 2020 Apr 1;80(7):1461-1474. (PMID: 32029550) Cancer Res. 2016 Sep 1;76(17):5040-53. (PMID: 27364557) Kidney Int. 2022 Jan;101(1):131-136. (PMID: 34555393) Trends Cell Biol. 2019 Mar;29(3):212-226. (PMID: 30594349) Cell. 2023 Jan 19;186(2):363-381.e19. (PMID: 36669472) Nat Genet. 2017 Aug;49(8):1261-1266. (PMID: 28650485) Nat Protoc. 2020 Aug;15(8):2413-2442. (PMID: 32690957) Nat Commun. 2021 Feb 8;12(1):863. (PMID: 33558489) Genes Cancer. 2015 Mar;6(3-4):129-43. (PMID: 26000096) Cancer Cell. 2021 Jun 14;39(6):827-844.e10. (PMID: 34129824) Nat Methods. 2017 Sep;14(9):865-868. (PMID: 28759029) Cancer Cell. 2007 May;11(5):421-9. (PMID: 17482132) J Pathol Clin Res. 2015 Apr;1(2):83-94. (PMID: 26052443) Clin Cancer Res. 2021 May 1;27(9):2636-2647. (PMID: 33622705) Nat Cell Biol. 2023 Feb;25(2):298-308. (PMID: 36658219) Mol Cancer Res. 2006 Nov;4(11):851-9. (PMID: 17114343) Oncogene. 2017 Jun 22;36(25):3505-3514. (PMID: 28135250) Nat Genet. 2012 Feb 12;44(3):323-7. (PMID: 22327514) Cell. 2017 Sep 21;171(1):163-178.e19. (PMID: 28844694) Nat Cell Biol. 2022 Aug;24(8):1192-1201. (PMID: 35941364) JCI Insight. 2018 Sep 20;3(18):. (PMID: 30232274) Mol Cell. 2022 Jun 2;82(11):2084-2097.e5. (PMID: 35483357) Front Oncol. 2022 Nov 24;12:1044707. (PMID: 36505823) Clin Cancer Res. 2022 Oct 14;28(20):4466-4478. (PMID: 35653119) Nat Med. 2018 May;24(5):541-550. (PMID: 29686425) Curr Protoc. 2021 Mar;1(3):e90. (PMID: 33780170) Physiol Rev. 2021 Jan 1;101(1):147-176. (PMID: 32466724) Cancer Res. 2017 Sep 1;77(17):4556-4561. (PMID: 28811330) Pharmacol Ther. 2021 May;221:107753. (PMID: 33259885) Cancer Cell. 2021 Aug 9;39(8):1150-1162.e9. (PMID: 34115987) Nat Rev Dis Primers. 2018 Jul 5;4(1):5. (PMID: 29977059) ISRN Oncol. 2011;2011:168712. (PMID: 22084725) Nat Rev Cancer. 2020 Mar;20(3):174-186. (PMID: 31980749) JCI Insight. 2020 Jul 9;5(13):. (PMID: 32544094) Cell Cycle. 2008 Jan 15;7(2):250-6. (PMID: 18256529) Am J Pathol. 1987 Oct;129(1):74-85. (PMID: 2821816) Mol Cell Proteomics. 2018 May;17(5):901-912. (PMID: 29386236) Nat Commun. 2020 Oct 9;11(1):5120. (PMID: 33037194) Cell. 2019 Aug 8;178(4):835-849.e21. (PMID: 31327527) Cancer Cell. 2023 Mar 13;41(3):374-403. (PMID: 36917948) Br J Cancer. 1982 Dec;46(6):848-55. (PMID: 6758829) Nat Med. 2019 Mar;25(3):367-376. (PMID: 30842674) NPJ Regen Med. 2019 Dec 2;4:22. (PMID: 31815001) Sci Adv. 2023 Feb 10;9(6):eade9238. (PMID: 36753540) Matrix Biol. 2016 Jan;49:10-24. (PMID: 26163349) J Transl Med. 2020 May 20;18(1):207. (PMID: 32434573) Nat Cancer. 2022 Jul;3(7):793-807. (PMID: 35883004) Nat Commun. 2019 Apr 3;10(1):1523. (PMID: 30944313) Cancer Discov. 2013 Oct;3(10):1190-205. (PMID: 23906982) Nat Rev Mol Cell Biol. 2020 Jun;21(6):341-352. (PMID: 32300252) Cancer Discov. 2022 Jan;12(1):31-46. (PMID: 35022204) Nat Rev Cancer. 2015 Aug;15(8):473-83. (PMID: 26156638) Nat Med. 2013 Sep;19(9):1104-9. (PMID: 24013756) Nat Rev Cancer. 2021 Apr;21(4):217-238. (PMID: 33589810) Cell Rep. 2020 Feb 11;30(6):1767-1779.e6. (PMID: 32049009) Nat Med. 2011 Jun 26;17(7):867-74. (PMID: 21706029) Cell Rep. 2015 Feb 24;10(7):1082-95. (PMID: 25704812) |
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 |