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Oncogene ; 39(4): 849-861, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31562394

RESUMEN

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.


Asunto(s)
Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/patología , Esferoides Celulares/patología , Tumor de Wilms/patología , Animales , Biomarcadores de Tumor/metabolismo , Técnicas de Cultivo de Célula , Preescolar , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Técnicas In Vitro , Lactante , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Masculino , Ratones Endogámicos NOD , Ratones SCID , Cultivo Primario de Células , Factores de Riesgo , Esferoides Celulares/metabolismo , Tumor de Wilms/genética , Tumor de Wilms/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
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