{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T07:28:59Z","timestamp":1788074939324,"version":"build-2784847793"},"posted":{"date-parts":[[2023,4,13]]},"group-title":"Cancer Biology","reference-count":65,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,4,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Tumor heterogeneity is a major driver of cancer progression. In epithelial-derived malignancies, carcinoma-associated fibroblasts (CAFs) contribute to tumor heterogeneity by depositing extracellular matrix (ECM) proteins that dynamically remodel the tumor microenvironment (TME). Ewing sarcomas (EwS) are histologically monomorphous, mesenchyme-derived tumors that are devoid of CAFs. Here we identify a previously uncharacterized subpopulation of transcriptionally distinct EwS tumor cells that deposit pro-tumorigenic ECM. Single cell analyses revealed that these CAF-like cells differ from bulk EwS cells by their upregulation of a matrisome-rich gene signature that is normally repressed by EWS::FLI1, the oncogenic fusion transcription factor that underlies EwS pathogenesis. Further, our studies showed that ECM-depositing tumor cells express the cell surface marker CD73, allowing for their isolation ex vivo and detection in situ. Spatial profiling of tumor xenografts and patient biopsies demonstrated that CD73\n                  <jats:sup>+<\/jats:sup>\n                  EwS cells and tumor cell-derived ECM are prevalent along tumor borders and invasive fronts. Importantly, despite loss of EWS::FLI1-mediated gene repression, CD73\n                  <jats:sup>+<\/jats:sup>\n                  EwS cells retain expression of EWS::FLI1 and the fusion-activated gene signature, as well as tumorigenic and proliferative capacities. Thus, EwS tumor cells can be reprogrammed to adopt CAF-like properties and these transcriptionally and phenotypically distinct cell subpopulations contribute to tumor heterogeneity by remodeling the TME.\n                <\/jats:p>","DOI":"10.1101\/2023.04.12.536619","type":"posted-content","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T14:30:11Z","timestamp":1681396211000},"source":"Crossref","is-referenced-by-count":5,"title":["Carcinoma-associated fibroblast-like tumor cells remodel the Ewing sarcoma tumor microenvironment"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9643-457X","authenticated-orcid":false,"given":"Emma D.","family":"Wrenn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3551-4429","authenticated-orcid":false,"given":"April 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