Renal carcinoma/kidney progenitor cell chimera organoid as a novel tumorigenesis gene discovery model

Disease Models & Mechanisms
Qi XuSeppo J Vainio

Abstract

Three-dimensional (3D) organoids provide a new way to model various diseases, including cancer. We made use of recently developed kidney-organ-primordia tissue-engineering technologies to create novel renal organoids for cancer gene discovery. We then tested whether our novel assays can be used to examine kidney cancer development. First, we identified the transcriptomic profiles of quiescent embryonic mouse metanephric mesenchyme (MM) and of MM in which the nephrogenesis program had been induced ex vivo The transcriptome profiles were then compared to the profiles of tumor biopsies from renal cell carcinoma (RCC) patients, and control samples from the same kidneys. Certain signature genes were identified that correlated in the developmentally induced MM and RCC, including components of the caveolar-mediated endocytosis signaling pathway. An efficient siRNA-mediated knockdown (KD) of Bnip3, Gsn, Lgals3, Pax8, Cav1, Egfr or Itgb2 gene expression was achieved in mouse RCC (Renca) cells. The live-cell imaging analysis revealed inhibition of cell migration and cell viability in the gene-KD Renca cells in comparison to Renca controls. Upon siRNA treatment, the transwell invasion capacity of Renca cells was also inhibited. Finally, w...Continue Reading

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Citations

May 28, 2019·Cells·Monica Vara-PerezPatrizia Agostinis
Jun 1, 2020·Cancer Metastasis Reviews·Vibha Singh, Christophe Lamaze
Nov 18, 2018·Journal of Cellular Physiology·Rahul MittalVasanti M Jhaveri
Mar 6, 2021·Veterinary Research·Bertrand Pain

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Datasets Mentioned

BETA
GSE53757

Methods Mentioned

BETA
transfection
PCR
biopsies
FACS
electrophoresis

Software Mentioned

R Bioconductor LIMMA package
Ensemble Base
Quantile
Ingenuity analysis
Ingenuity
IncuCyte

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