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 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.

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Publication Details

Journal
Translational Oncology
Published
2024-12-30
DOI
https://doi.org/10.1016/j.tranon.2024.102263
Citations
1
Primary Topic
Renal and related cancers
Type
article
Field-Weighted Citation Impact
0.23

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article

Wilms tumor primary cultures capture phenotypic heterogeneity and facilitate preclinical screening

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1 citations
Translational Oncology
Renal and related cancers
0.23
article

Wilms tumor primary cultures capture phenotypic heterogeneity and facilitate preclinical screening

Sabrina Bausenwein, Sheena Warman, Norbert M. Graf, Karen Ernestus, Jörg Fuchs, Nils Welter, Jarno Drost, Rhoikos Furtwängler, Jenny Wegert, Christin Linderkamp, Alireza Paikari, Sam Behjati, Silke Appenzeller, Taryn D. Treger, Manfred Gessler, Lisa Götz, Dominik T. Schneider, Christian Vokuhl
article en
1 citations

Abstract

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.

Translational OncologyVol. 52
Witten/Herdecke University (DE), University of Würzburg (DE), University Hospital Bonn (DE), University Hospital of Bern (CH), Cambridge University Hospitals NHS Foundation Trust (GB), Medizinische Hochschule Hannover (DE), Comprehensive Cancer Center Mainfranken (DE), University Children's Hospital Tübingen (DE), Universitätsklinikum Würzburg (DE), Princess Máxima Center (NL), Charité - Universitätsmedizin Berlin (DE), Saarland University (DE)
Wilhelm Sander-Stiftung, Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, Little Princess Trust
Zero hunger
Openalex Percentile: Top 40%
Renal and related cancers
0.23
DOIOpen Access PDFOpenAlex
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