%0 Journal Article
%T Deciphering the role of FUS::DDIT3 expression and tumor microenvironment in myxoid liposarcoma development.
%A Ranji P
%A Jonasson E
%A Andersson L
%A Filges S
%A Luna Santamaría M
%A Vannas C
%A Dolatabadi S
%A Gustafsson A
%A Myklebost O
%A Håkansson J
%A Fagman H
%A Landberg G
%A Åman P
%A Ståhlberg A
%J J Transl Med
%V 22
%N 1
%D 2024 Apr 26
%M 38671504
%F 8.44
%R 10.1186/s12967-024-05211-w
%X <B>BACKGROUND: </B>Myxoid liposarcoma (MLS) displays a distinctive tumor microenvironment and is characterized by the FUS::DDIT3 fusion oncogene, however, the precise functional contributions of these two elements remain enigmatic in tumor development.<BR><B>METHODS: </B>To study the cell-free microenvironment in MLS, we developed an experimental model system based on decellularized patient-derived xenograft tumors. We characterized the cell-free scaffold using mass spectrometry. Subsequently, scaffolds were repopulated using sarcoma cells with or without FUS::DDIT3 expression that were analyzed with histology and RNA sequencing.<BR><B>RESULTS: </B>Characterization of cell-free MLS scaffolds revealed intact structure and a large variation of protein types remaining after decellularization. We demonstrated an optimal culture time of 3 weeks and showed that FUS::DDIT3 expression decreased cell proliferation and scaffold invasiveness. The cell-free MLS microenvironment and FUS::DDIT3 expression both induced biological processes related to cell-to-cell and cell-to-extracellular matrix interactions, as well as chromatin remodeling, immune response, and metabolism. Data indicated that FUS::DDIT3 expression more than the microenvironment determined the pre-adipocytic phenotype that is typical for MLS.<BR><B>CONCLUSIONS: </B>Our experimental approach opens new means to study the tumor microenvironment in detail and our findings suggest that FUS::DDIT3-expressing tumor cells can create their own extracellular niche.