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- Title
Deciphering the role of FUS::DDIT3 expression and tumor microenvironment in myxoid liposarcoma development.
- Authors
Ranji, Parmida; Jonasson, Emma; Andersson, Lisa; Filges, Stefan; Luna Santamaría, Manuel; Vannas, Christoffer; Dolatabadi, Soheila; Gustafsson, Anna; Myklebost, Ola; Håkansson, Joakim; Fagman, Henrik; Landberg, Göran; Åman, Pierre; Ståhlberg, Anders
- Abstract
Background: 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. Methods: 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. Results: 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. Conclusions: 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.
- Subjects
GENE expression; TUMOR microenvironment; RNA sequencing; PHENOTYPES; MASS spectrometry; LIPOSARCOMA
- Publication
Journal of Translational Medicine, 2024, Vol 22, Issue 1, p1
- ISSN
1479-5876
- Publication type
Article
- DOI
10.1186/s12967-024-05211-w