Characterisation of a Novel Cell Line (ICR-SS-1) Established from a Patient-Derived Xenograft of Synovial Sarcoma

Abstract

Synovial sarcoma is a rare translocation-driven cancer with poor survival outcomes, particularly in the advanced setting. Previous synovial sarcoma preclinical studies have relied on a small panel of cell lines which suffer from the limitation of genomic and phenotypic drift as a result of being grown in culture for decades. Patient-derived xenografts (PDX) are a valuable tool for preclinical research as they retain many histopathological features of their originating human tumour; however, this approach is expensive, slow, and resource intensive, which hinders their utility in large-scale functional genomic and drug screens. To address some of these limitations, in this study, we have established and characterised a novel synovial sarcoma cell line, ICR-SS-1, which is derived from a PDX model and is amenable to high-throughput drug screens. We show that ICR-SS-1 grows readily in culture, retains the pathognomonic SS18::SSX1 fusion gene, and recapitulates the molecular features of human synovial sarcoma tumours as shown by proteomic profiling. Comparative analysis of drug response profiles with two other established synovial sarcoma cell lines (SYO-1 and HS-SY-II) finds that ICR-SS-1 harbours intrinsic resistance to doxorubicin and is sensitive to targeted inhibition of several oncogenic pathways including the PI3K-mTOR pathway. Collectively, our studies show that the ICR-SS-1 cell line model may be a valuable preclinical tool for studying the biology of anthracycline-resistant synovial sarcoma and identifying new salvage therapies following failure of doxorubicin.

Synovial Sarcoma Preclinical Modeling: Integrating Transgenic Mouse Models and Patient-Derived Models for Translational Research

“…All three cell lines were resistant to Pazopanib (IC50 > 5 µM). Only three compounds, the dual PI3K-mTOR inhibitor NVP-BEZ235, the PLK1 inhibitor BI 2536, and the BET bromodomain inhibitor JQ1, were effective in all three cell lines, indicating the underlying pathways as possible shared vulnerabilities among SyS [86].…”

“…Finally, SyS PDXs are being also used for the establishment of new SyS cell lines [40,85,86] that will be reported in the next paragraph.…”

“…Interestingly, the human SyS cell line KU-SS-1 was derived from a PDX at the third in vivo passage [85] and, recently, two additional new SyS cell lines, SS-PDX [40] and ICR-SS-1 [86], not yet included in the Cellosaurus database, were independently obtained from the same publicly available SyS PDX J000104314 distributed from The Jackson Laboratory biorepository [86]. Hopefully the establishment of new, clinically relevant SyS cell lines derived from SyS PDX models will increase in the near future and will expand the collection of SyS in vitro/in vivo preclinical models.…”