A novel mouse model for human synovial sarcoma expressing SS18-SSX1

ABSTRACT: SS18-SSX fusion proteins play a central role in synovial sarcoma development, however, genetic network and mechanisms of synovial sarcomagenesis remain largely unknown. To clarify such unknown mechanisms, we have established a new ex vivo mouse model for synovial sarcoma, using retrovirus-mediated gene transfer of SS18-SSX1 to mouse embryonic mesenchymal cells followed by subcutaneous transplantation into nude mice. This approach successfully induced subcutaneous tumors in 100% of recipients, showing invasive proliferation of short spindle tumor cells with occasional biphasic appearance. Cytokeratin expression was observed in epithelial components in tumors and expression of TLE1 and BCL2 was also shown. Gene expression profiling indicates modulation of the SWI/SNF pathway by introduction of SS18-SSX1 into mesenchymal cells, and upregulation of Tle1 and Atf2 in tumors. Collectively, these findings indicate the model exhibits typical phenotypes of human synovial sarcoma. Retroviral tagging of the tumor identified 15 common retroviral integration sites with the Dnm3 locus as the most frequent in 30 mouse synovial sarcomas. Up-regulation of micro RNAs miR-199a2 and miR-214 within the Dnm3 locus was observed. Co-introduction of SS18-SSX1 and miR-214 indeed accelerated sarcoma onset, indicating that miR-214 is a cooperative onco-miR in synovial sarcomagenesis. miR-214 functions in the cell non-autonomous manner, promoting cytokine gene expression such as Cxcl15/IL8. We have succeeded to generate a novel mouse model for human synovial sarcoma. As miR-214 overexpression in human synovial sarcoma was reported, our results underscore the important role of miR-214 in tumor development and disease progression. We used microarrays to detail the global program of gene expression in mouse synovial sarcoma and embryonic mesenchymal cells

ORGANISM(S): Mus musculus

PROVIDER: GSE141251 | GEO | 2020/03/30

REPOSITORIES: GEO