Generation of an EHE Extended Primary Cell Culture

Epithelioid hemangioendothelioma (EHE) is a difficult to treat vascular sarcoma defined by mutually exclusive TAZ-CAMTA1 (TC) or YAP-TFE3 (YT) fusion proteins. Human cell line systems are needed to dissect the mechanisms underpinning this cancer and evaluate new therapeutic approaches, however human EHE cell lines have yet to be developed. We have developed a method to generate EHE extended primary cell cultures from human samples and have characterized them. Important aspects are conserved between the tumors and cell cultures including detection of the fusion protein by RT-PCR, expression of CAMTA1 by single cell RNA-Seq, and western blot. The cell cultures display many established characteristics of EHE including proliferation, the ability to grow in an anchorage independent manner and susceptibility to TEAD inhibition. Whole genome sequencing (WGS) showed links to epigenetic modifying complexes known to be recruited by the fusion proteins. RNA-Seq demonstrated upregulation of pathways known to be involved in the progression of the disease including PI3K-Akt signaling, ECM receptor interaction, Hippo signaling pathway, focal adhesion, and proteoglycans in cancer. Continued efforts to generate EHE cultures will aid in the mechanistic understanding of the disease and serve as a platform for testing new therapeutic avenues.