Construction and Characterization of Paired Patient-Derived Cell Models for Solitary Fibrous Tumors (SFTs)

Introduction: Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm that can arise across a wide range of anatomical locations, most commonly within the thoracic cavity, including the pleura. Surgical resection and radiotherapy are often first-line treatments for SFT. However, tumors that are not amenable to these conventional approaches require systemic therapy, for which effective options remain limited. In 2013, the NAB2::STAT6 fusion gene was discovered as the critical oncogenic driver of SFT. Nevertheless, the underlying molecular mechanisms by which the NAB2::STAT6 fusion event drives cancer progression remain largely unknown, primarily due to the lack of proper SFT and control cell models. Aims: To address this challenge, we used the SFT patient-derived cell line, INT-SFT, and performed short hairpin RNA (shRNA)-mediated downregulation to interrogate fusion-associated effects. Results: Phenotypic assays confirmed the oncogenic effects of the NAB2::STAT6 fusion transcript. Next, using transcriptomic and proteomic analyses, we identified genes and proteins regulated by the NAB2::STAT6 fusion and delineated its effects on key signaling pathways. Conclusions: Taken together, our SFT cell models, derived from the same genetic and clinical background but with different expression levels of the fusion transcript, represent a valuable resource for studying etiology and exploring novel therapeutics for SFTs.