Wilms tumor primary cultures capture phenotypic heterogeneity and facilitate preclinical screening
Wilms tumors (WT) are characterized by variable contributions of blastemal, epithelial and stromal elements, reflecting their diverse cellular origins and genetic drivers. In vitro models remain rare, despite a growing need to better characterize tumor biology and evaluate new treatments. Using thre...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523324003899 |
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| author | Lisa Götz Jenny Wegert Alireza Paikari Silke Appenzeller Sabrina Bausenwein Christian Vokuhl Taryn D. Treger Jarno Drost Christin Linderkamp Dominik T. Schneider Karen Ernestus Steven W. Warman Jörg Fuchs Nils Welter Norbert Graf Sam Behjati Rhoikos Furtwängler Manfred Gessler |
| author_facet | Lisa Götz Jenny Wegert Alireza Paikari Silke Appenzeller Sabrina Bausenwein Christian Vokuhl Taryn D. Treger Jarno Drost Christin Linderkamp Dominik T. Schneider Karen Ernestus Steven W. Warman Jörg Fuchs Nils Welter Norbert Graf Sam Behjati Rhoikos Furtwängler Manfred Gessler |
| author_sort | Lisa Götz |
| collection | DOAJ |
| description | Wilms tumors (WT) are characterized by variable contributions of blastemal, epithelial and stromal elements, reflecting their diverse cellular origins and genetic drivers. In vitro models remain rare, despite a growing need to better characterize tumor biology and evaluate new treatments. Using three approaches, we have now established a large collection of long-term cultures that represent this diversity. Adherent WT cultures are predominated by stromal cells, 3D spheroids model blastema, and patient-derived organoid cultures of both tumor and healthy kidney tissue result in the preferential growth of epithelial cells. Adherent, spheroid and organoid cultures are also clearly distinguishable by their transcriptome. Preclinical drug screening experiments revealed sensitivity to a range of inhibitors, that are highly effective in other childhood solid tumors. Sensitivity was related to MYCN status, a marker associated with adverse outcome across human cancers including WT. The combination of the three culture techniques represents a promising tool to both explore tumor heterogeneity in vitro and to facilitate characterization of candidate driver genes, in order to improve treatment regimens in the future. |
| format | Article |
| id | doaj-art-a3a459fc4322480da30c9a68dfb36b31 |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-a3a459fc4322480da30c9a68dfb36b312025-01-22T05:41:32ZengElsevierTranslational Oncology1936-52332025-02-0152102263Wilms tumor primary cultures capture phenotypic heterogeneity and facilitate preclinical screeningLisa Götz0Jenny Wegert1Alireza Paikari2Silke Appenzeller3Sabrina Bausenwein4Christian Vokuhl5Taryn D. Treger6Jarno Drost7Christin Linderkamp8Dominik T. Schneider9Karen Ernestus10Steven W. Warman11Jörg Fuchs12Nils Welter13Norbert Graf14Sam Behjati15Rhoikos Furtwängler16Manfred Gessler17Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, Julius-Maximilians-University Würzburg, Würzburg, GermanyTheodor-Boveri-Institute/Biocenter, Developmental Biochemistry, Julius-Maximilians-University Würzburg, Würzburg, GermanyTheodor-Boveri-Institute/Biocenter, Developmental Biochemistry, Julius-Maximilians-University Würzburg, Würzburg, GermanyComprehensive Cancer Center Mainfranken, University Hospital of Würzburg, Würzburg, GermanyTheodor-Boveri-Institute/Biocenter, Developmental Biochemistry, Julius-Maximilians-University Würzburg, Würzburg, GermanySection of Pediatric Pathology, Department of Pathology, University Hospital Bonn, Bonn, GermanyWellcome Sanger Institute, Hinxton, UK; Department of Pediatrics, University of Cambridge, Cambridge CB2 0QQ, UK; Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UKPrincess Máxima Center for Pediatric Oncology, Utrecht, NetherlandsDepartment of Pediatric Hematology and Oncology, Hannover Medical School (MHH), Hannover, GermanyClinic of Pediatrics, Klinikum Dortmund, University Witten/Herdecke, GermanyComprehensive Cancer Center Mainfranken, University Hospital of Würzburg, Würzburg, Germany; Department of Pathology, University of Würzburg, Würzburg, GermanyClinic of Pediatric Surgery, Charité – University Hospital Berlin, Berlin, Germany; Department of Pediatric Surgery and Pediatric Urology, University Children's Hospital, Tuebingen, GermanyDepartment of Pediatric Surgery and Pediatric Urology, University Children's Hospital, Tuebingen, GermanyDepartment of Pediatric Hematology and Oncology, Saarland University Hospital, Homburg, GermanyDepartment of Pediatric Hematology and Oncology, Saarland University Hospital, Homburg, GermanyWellcome Sanger Institute, Hinxton, UK; Department of Pediatrics, University of Cambridge, Cambridge CB2 0QQ, UK; Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UKDepartment of Pediatric Hematology and Oncology, Saarland University Hospital, Homburg, Germany; Pediatric Hematology and Oncology, Dep. of Pediatrics, Bern University Hospital, University of Bern, Inselspital, SwitzerlandTheodor-Boveri-Institute/Biocenter, Developmental Biochemistry, Julius-Maximilians-University Würzburg, Würzburg, Germany; Comprehensive Cancer Center Mainfranken, University Hospital of Würzburg, Würzburg, Germany; Corresponding authorWilms tumors (WT) are characterized by variable contributions of blastemal, epithelial and stromal elements, reflecting their diverse cellular origins and genetic drivers. In vitro models remain rare, despite a growing need to better characterize tumor biology and evaluate new treatments. Using three approaches, we have now established a large collection of long-term cultures that represent this diversity. Adherent WT cultures are predominated by stromal cells, 3D spheroids model blastema, and patient-derived organoid cultures of both tumor and healthy kidney tissue result in the preferential growth of epithelial cells. Adherent, spheroid and organoid cultures are also clearly distinguishable by their transcriptome. Preclinical drug screening experiments revealed sensitivity to a range of inhibitors, that are highly effective in other childhood solid tumors. Sensitivity was related to MYCN status, a marker associated with adverse outcome across human cancers including WT. The combination of the three culture techniques represents a promising tool to both explore tumor heterogeneity in vitro and to facilitate characterization of candidate driver genes, in order to improve treatment regimens in the future.http://www.sciencedirect.com/science/article/pii/S1936523324003899Wilms tumorNephroblastomaOrganoid cultureDrug screeningMYCN |
| spellingShingle | Lisa Götz Jenny Wegert Alireza Paikari Silke Appenzeller Sabrina Bausenwein Christian Vokuhl Taryn D. Treger Jarno Drost Christin Linderkamp Dominik T. Schneider Karen Ernestus Steven W. Warman Jörg Fuchs Nils Welter Norbert Graf Sam Behjati Rhoikos Furtwängler Manfred Gessler Wilms tumor primary cultures capture phenotypic heterogeneity and facilitate preclinical screening Translational Oncology Wilms tumor Nephroblastoma Organoid culture Drug screening MYCN |
| title | Wilms tumor primary cultures capture phenotypic heterogeneity and facilitate preclinical screening |
| title_full | Wilms tumor primary cultures capture phenotypic heterogeneity and facilitate preclinical screening |
| title_fullStr | Wilms tumor primary cultures capture phenotypic heterogeneity and facilitate preclinical screening |
| title_full_unstemmed | Wilms tumor primary cultures capture phenotypic heterogeneity and facilitate preclinical screening |
| title_short | Wilms tumor primary cultures capture phenotypic heterogeneity and facilitate preclinical screening |
| title_sort | wilms tumor primary cultures capture phenotypic heterogeneity and facilitate preclinical screening |
| topic | Wilms tumor Nephroblastoma Organoid culture Drug screening MYCN |
| url | http://www.sciencedirect.com/science/article/pii/S1936523324003899 |
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