ORIGINAL RESEARCH article
Front. Oncol.
Sec. Pediatric Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1589773
This article is part of the Research TopicCurrent Status And Recent Advances In Preclinical Models For Rare CancersView all 6 articles
Establishing Preclinical Models for Clear Cell Sarcoma of Soft Tissue
Provisionally accepted
BINGBING LI*
Jake Piesner- Oregon Health and Science University, Portland, United States
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Clear cell sarcoma of soft tissue (CCSST) is a rare but deadly soft tissue sarcoma driven by fusion proteins. It is characterized by translocations t(12;22) or t(2;22), leading to fusion formation between Ewing Sarcoma Breakpoint Region 1 (EWSR1) and activating transcription factor 1(ATF1) or cAMP-response element-binding protein (CREB), respectively. CREB and ATF1 are members of CREB family transcription factor that respond to elevated level of intracellular cAMP. While the transcription activity of CREB and ATF1 depends on the phosphorylation, type 1 EWSR1-ATF1 fusion is a constitutively active transcription factor. Besides type 1 fusion, 6 additional EWSR1-ATF1 and one EWSR1-CREB fusions have been discovered from CCSST patients. However, it is unknown if these other fusions are constitutively active. We show that type 2, 3 and 7 as well as EWSR1-CREB are also constitutively active while type 4, 5 and 6 are not. Metastasis is a major prognosis factor for CCSST patients, however, no scalable preclinical models of CCSST metastasis have been developed.We evaluated the invasion potential of a panel of patient-derived cell lines and developed both in vitro and in vivo models of CCSST metastasis based on CCS292 cell line. The suite of preclinical assays and models developed here are valuable tools for assessing potential therapeutics for CCSST patients.
Keywords: Clear cell sarcoma, CCSST, EWSR1, ATF1, CREB
Received: 07 Mar 2025; Accepted: 26 May 2025.
Copyright: © 2025 LI and Piesner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: BINGBING LI, Oregon Health and Science University, Portland, United States
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