| Autor: |
Parmida Ranji, Emma Jonasson, Lisa Andersson, Stefan Filges, Manuel Luna Santamaría, Christoffer Vannas, Soheila Dolatabadi, Anna Gustafsson, Ola Myklebost, Joakim Håkansson, Henrik Fagman, Göran Landberg, Pierre Åman, Anders Ståhlberg |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Journal of Translational Medicine, Vol 22, Iss 1, Pp 1-14 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1479-5876 |
| DOI: |
10.1186/s12967-024-05211-w |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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