In vitro models represent a critical tool in cancer research to study tumor biology and to evaluate new treatment options. Unfortunately, there are no effective preclinical models available that represent Wilms tumor (WT) – the most common pediatric renal tumor. Especially the high-risk blastemal WT subtype is not represented by the few primary cell lines established until now. Here, we describe a new 3D approach for in vitro cultivation of blastemal WT cells, where primary cultures grown in suspension as spheroids could be propagated long-term. Besides blastemal cultures, we could generate spheroids representing epithelial and stromal WT. Spheroid cultures were analyzed by immunohistochemistry in comparison to corresponding tumor sections and were further characterized by RNA sequencing. Histological appearance of spheroids resembled the original tumor and they expressed marker genes characteristic of early renal development and blastemal WT elements. The cultures were amenable to genetic manipulation and they formed xenograft tumors, which resemble the primary human tumor. This collection of WT spheroids that carry different genetic drivers forms a long-sought tool for drug testing and in vitro modeling.
Oncogene. 2019 Sep 27 [Epub ahead of print]
Jenny Wegert, Lisa Zauter, Silke Appenzeller, Christoph Otto, Sabrina Bausenwein, Christian Vokuhl, Karen Ernestus, Rhoikos Furtwängler, Norbert Graf, Manfred Gessler
Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, University of Wuerzburg, Wuerzburg, Germany., Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Wuerzburg, Germany., Experimental Surgery, Department of General, Visceral, Vascular, and Pediatric Surgery, University Hospital of Wuerzburg, Wuerzburg, Germany., Kiel Pediatric Tumor Registry, Section of Pediatric Pathology, Department of Pathology, University Hospital of Kiel, Kiel, Germany., Institute for Pathology, University of Wuerzburg, Wuerzburg, Germany., Pediatric Oncology and Hematology, Children’s Hospital, Saarland University and Saarland University Medical Centre, Homburg, Germany., Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, University of Wuerzburg, Wuerzburg, Germany. .