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.