EHE cell cultures: a platform for mechanistic and therapeutic investigation

Nicholas Scalora; Gillian DeWane; Yuliia Drebot; Ali A. Khan; Souradip Sinha; Krishnendu Ghosh; Denise Robinson; Patricia Cogswell; Andrew M. Bellizzi; Anthony N. Snow; Patrick Breheny; Michael S. Chimenti; Munir R. Tanas

doi:10.1101/2025.03.24.644191

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EHE cell cultures: a platform for mechanistic and therapeutic investigation

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EHE cell cultures: a platform for mechanistic and therapeutic investigation

Nicholas Scalora, Gillian DeWane, Yuliia Drebot, Ali A. Khan, Souradip Sinha, Krishnendu Ghosh, Denise Robinson, Patricia Cogswell, Andrew M. Bellizzi, Anthony N. Snow, …

bioRxiv

Cold Spring Harbor Laboratory, 1.1

03/27/2025

DOI: 10.1101/2025.03.24.644191

PMCID: PMC11974726

PMID: 40196670

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https://doi.org/10.1101/2025.03.24.644191View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Epithelioid hemangioendothelioma (EHE) is a difficult to treat vascular sarcoma defined by TAZ- CAMTA1 or YAP-TFE3 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 EHE primary cell cultures will aid in the mechanistic understanding of this sarcoma and serve as a model system to test new therapeutic approaches.

Cancer Biology

Details

Title: Subtitle: EHE cell cultures: a platform for mechanistic and therapeutic investigation
Creators: Nicholas Scalora - University of Iowa
Gillian DeWane - University of Iowa
Yuliia Drebot - University of Iowa
Ali A. Khan - Cancer Biology Graduate Program, University of Iowa
Souradip Sinha - University of Iowa
Krishnendu Ghosh - University of Iowa
Denise Robinson - The EHE Foundation
Patricia Cogswell - The EHE Foundation
Andrew M. Bellizzi - University of Iowa
Anthony N. Snow - University of Iowa
Patrick Breheny - University of Iowa
Michael S. Chimenti - University of Iowa
Munir R. Tanas - Holden Comprehensive Cancer Center, University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
Edition: 1.1
DOI: 10.1101/2025.03.24.644191
PMID: 40196670
PMCID: PMC11974726
NLM abbreviation: bioRxiv
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory
Number of pages: 47
Language: English
Date posted: 03/27/2025
Academic Unit: Pathology; Biostatistics; Iowa Institute of Human Genetics
Record Identifier: 9984808539202771

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