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Deciphering the rol...
Deciphering the role of FUS::DDIT3 expression and tumor microenvironment in myxoid liposarcoma development
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- Ranji, Parmida (author)
- University of Gothenburg, Sweden
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- Jonasson, Emma (author)
- University of Gothenburg, Sweden
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- Andersson, Lisa (author)
- University of Gothenburg, Sweden
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- Filges, Stefan (author)
- University of Gothenburg, Sweden
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- Luna Santamaría, Manuel (author)
- University of Gothenburg, Sweden
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- Vannas, Christoffer (author)
- University of Gothenburg, Sweden; Sahlgrenska University Hospital, Sweden
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- Dolatabadi, Soheila (author)
- University of Gothenburg, Sweden
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- Gustafsson, Anna (author)
- University of Gothenburg, Sweden
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- Myklebost, Ola (author)
- Oslo University Hospital, Norway; University of Bergen, Norway
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- Håkansson, Joakim (author)
- RISE,Metodik för produktframtagning,University of Gothenburg, Sweden
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- Fagman, Henrik (author)
- University of Gothenburg, Sweden; Sahlgrenska University Hospital, Sweden
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- Landberg, Göran (author)
- University of Gothenburg, Sweden; Sahlgrenska University Hospital, Sweden
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- Åman, Pierre (author)
- University of Gothenburg, Sweden; Sahlgrenska University Hospital, Sweden
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- Ståhlberg, Anders (author)
- University of Gothenburg, Sweden; Sahlgrenska University Hospital, Sweden
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(creator_code:org_t)
- BioMed Central Ltd, 2024
- 2024
- English.
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In: Journal of Translational Medicine. - : BioMed Central Ltd. - 1479-5876. ; 22
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https://ri.diva-port... (primary) (Raw object)
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Animals; Cell Line
- Tumor; Cell Proliferation; Cell-Free System; Extracellular Matrix; Gene Expression Regulation
- Neoplastic; Humans; Liposarcoma
- Myxoid; Mice; Oncogene Proteins
- Fusion; RNA-Binding Protein FUS; Tissue Scaffolds; Tumor Microenvironment; eosin; growth arrest and DNA damage inducible protein 153; hematoxylin; HLA antigen; major histocompatibility antigen class 2; RNA binding protein FUS; FUS protein
- human; FUS-DDIT3 fusion protein
- human; oncogene fusion protein; RNA binding protein FUS; adipogenesis; animal cell; animal experiment; animal model; antigen presentation; Article; cell adhesion; cell culture; cell cycle; cell growth; cell infiltration; cell interaction; cell invasion; cell migration; cell proliferation; chromatin assembly and disassembly; controlled study; decellularization; down regulation; endocytosis; experimental model; extracellular matrix; female; functional enrichment analysis; gene expression; gene expression profiling; gene fusion; genetic transcription; glycolysis; histology; HT-1080 cell line; human; human cell; immune response; in vivo study; liquid chromatography-mass spectrometry; mass spectrometry; metabolism; mouse; myxosarcoma; nonhuman; nucleotide metabolism; oncogene; phenotype; protein expression; proteomics; RNA extraction; RNA sequencing; RNA synthesis; sarcoma cell; single cell RNA seq; tumor cell; tumor microenvironment; tumor xenograft; upregulation; animal; cell free system; chemistry; gene expression regulation; genetics; pathology; tumor cell line
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Ranji, Parmida
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Jonasson, Emma
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Andersson, Lisa
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Filges, Stefan
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Luna Santamaría, ...
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Vannas, Christof ...
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Dolatabadi, Sohe ...
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Gustafsson, Anna
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Myklebost, Ola
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Håkansson, Joaki ...
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Fagman, Henrik
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Landberg, Göran
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Åman, Pierre
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Ståhlberg, Ander ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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Journal of Trans ...
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RISE