Journal article
EHE cell cultures are a platform for mechanistic and therapeutic investigation
Scientific reports, Vol.15(1), 35516
10/10/2025
DOI: 10.1038/s41598-025-19453-1
PMCID: PMC12514230
PMID: 41073554
Abstract
Epithelioid hemangioendothelioma (EHE) is a difficult to treat vascular sarcoma defined by TAZ-CAMTA1 (TC) or YAP-TFE3 (YT) fusion proteins. Human cell lines needed to further understand the pathogenesis of EHE have been lacking. Herein, we describe a method to generate EHE extended primary cell cultures. An integrated multi -omic and functional approach was used to characterize these cultures. The cell cultures, relatively homogenous by single cell RNA-Seq, demonstrated established characteristics of EHE including increased proliferation, anchorage independent growth, as well as the overall gene expression profile and secondary genetic alterations seen in EHE. Whole genome sequencing (WGS) identified links to epigenetic modifying complexes, metabolic processes, and pointed to the importance of the extracellular matrix (ECM) in these tumors. Bulk RNA-Seq demonstrated upregulation of pathways including PI3K-Akt signaling, ECM/ECM receptor interaction, and the Hippo signaling pathway. Development of these extended primary cell cultures allowed for single-cell profiling which demonstrated different cell compartments within the cultures. Furthermore, the cultures served as a therapeutic platform to test the efficacy of TEAD inhibitors in vitro. Overall, the development of primary EHE cell cultures will aid in the mechanistic understanding of this sarcoma and serve as a model system to test new therapeutic approaches.
Details
- Title: Subtitle
- EHE cell cultures are a platform for mechanistic and therapeutic investigation
- Creators
- Nicholas Scalora - University of IowaGillian DeWane - University of IowaYuliia Drebot - University of IowaAli A Khan - Cancer Biology Graduate Program, University of Iowa, Iowa, IA, USASouradip Sinha - University of IowaKrishnendu Ghosh - University of IowaDenise Robinson - The EHE Foundation, Hobart, WI, USAPatricia Cogswell - The EHE Foundation, Hobart, WI, USAAndrew M Bellizzi - University of IowaAnthony N Snow - University of IowaPatrick Breheny - University of Iowa, BiostatisticsMichael S Chimenti - University of IowaMunir R Tanas - Veterans Health Administration
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.15(1), 35516
- DOI
- 10.1038/s41598-025-19453-1
- PMID
- 41073554
- PMCID
- PMC12514230
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- NATURE PORTFOLIO
- Grant note
- I01 BX003644 / BLRD VA R01 CA237031 / NCI NIH HHS Predoctoral fellowship / EHE Foundation 1 I01 BX003644-01 / Veterans Health Administration Merit Review Program 1 R01 CA237031-01A1 / National Institutes of Health, National Cancer Institute P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 10/10/2025
- Academic Unit
- Pathology; Biostatistics; Iowa Institute of Human Genetics
- Record Identifier
- 9985014872202771
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