Gene expression profiles associated with myxoid liposarcoma scaffold culture compared to monolayer growth and effect of fusion oncogene FUS-DDIT3
Myxoid liposarcoma (MLS) is the second most common type of liposarcoma and is characterized by the fusion oncogene FUS-DDIT3 or the less common EWSR1-DDIT3. FUS-DDIT3 is causative in tumor development, but the molecular function of FUS-DDIT3 remains largely unknown. In addition, the tumor microenvironment is important in MLS development. However, due to a lack of relevant experimental model systems, it has been challenging to examine the microenvironmental impact in MLS development. Therefore, we have developed an in vivo-like experimental model system utilizing cell-free scaffolds derived from myxoid liposarcoma patient-derived xenograft tumors that can be repopulated with tumor cells. To study the effect of FUS-DDIT3 expression in combination with the MLS microenvironment, we analyzed MLS cell lines as well as fibrosarcoma cells with and without ectopic FUS-DDIT3 expression cultured in scaffolds using cells cultured in monolayers as reference. We identified several gene networks and processes that are uniquely associated with FUS-DDIT3 expression as well as microenvironment. The use of in vivo-like experimental systems opens new possibilities to understand tumor development and develop treatments. Overall design: Five cell lines were cultured in scaffolds and monolayer (2D) in 3-5 replicates and analyzed using RNA sequencing: Two MLS cell lines, 1765-92 and 2645-94, as well as HT1080 fibrosarcoma cells with and without fusion oncogene FUS-DDIT3 including native HT1080 cells, HT1080 cells expressing EGFP and HT1080 cells expressing FUS-DDIT3-EGFP.