Deciphering the role of FUS::DDIT3 expression and tumor microenvironment in myxoid liposarcoma developmentShow others and affiliations
2024 (English)In: Journal of Translational Medicine, E-ISSN 1479-5876, Vol. 22, article id 389
Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
BioMed Central Ltd , 2024. Vol. 22, article id 389
Keywords [en]
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
National Category
Cell and Molecular Biology Cancer and Oncology
Identifiers
URN: urn:nbn:se:ri:diva-73289DOI: 10.1186/s12967-024-05211-wScopus ID: 2-s2.0-85191402673OAI: oai:DiVA.org:ri-73289DiVA, id: diva2:1860400
Funder
Stiftelsen Assar Gabrielssons fondRegion Västra GötalandSwedish Cancer Society, 2022-2080; 2022-2214Swedish Childhood Cancer Foundation, 2022-0030Swedish Research Council, 2021-01008; 2019-01273Vinnova, 2017-03737Sjöberg FoundationWilhelm och Martina Lundgrens Vetenskapsfond
Note
Open access funding provided by University of Gothenburg. This research was funded by Assar Gabrielssons Research Foundation; Johan Jansson Foundation for Cancer Research; Region Västra Götaland, Sweden; Swedish Cancer Society (2022-2080 and 2022-2214); Swedish Childhood Cancer Foundation (2022-0030); Swedish Research Council (2021-01008 and 2019-01273); the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (965065 and 965580) and Sweden's Innovation Agency (2017-03737); the Sjöberg Foundation and Wilhelm and Martina Lundgren Foundation for Scientific Research.
2024-05-242024-05-242025-09-23Bibliographically approved