GSE47356 A Patient-derived In Vitro – In Vivo Preclinical Model of Renal Cell Carcinoma

Contributors : Matthias Saar ; Hongjuan Zhao ; Alan E Thong ; Alexandre Ingels ; Maija P Valta ; Sarah R Young ; Rosalie Nolley ; Jennifer Santos ; Donna M Peehl
Series Type : Expression profiling by array
Organism : Homo sapiens

Purpose: Authentic preclinical models of renal cell carcinoma (RCC) are lacking. We aimed to establish and characterize primary RCC cultures and demonstrate the feasibility of evaluating drug responses in vitro and in vivo.
Materials and Methods: Previously published methodology, with minor modifications, was used to establish, cryopreserve, and serially passage RCC cells from nephrectomy and tumorgraft specimens. Cells were characterized for immuno- and molecular phenotype by immunochemistry, DNA sequencing and gene expression profiling. Tumorigenic potential was evaluated by implanting cells under the renal capsule of immunocompromised mice. The ability to monitor xenograft growth by magnetic resonance imaging (MRI) was investigated. Responses to a tyrosine kinase inhibitor (TKI) and an mTOR inhibitor were measured.
Results: Primary cultures were successfully established from 11 clear cell and 1 chromophobe RCC, cryopreserved and serially passaged. Retention of immuno- and molecular phenotypes was demonstrated. Cultured cells formed xenografts in mice that could be measured by MRI. Patient-specific responses to drugs were observed in vitro and response to an TKI was confirmed in vivo.
Conclusions: Our study is the first to show the derivation of primary cultures from RCC tumorgrafts, and to demonstrate the ability of primary RCC cultures to generate xenografts in mice. Our results suggest the feasibility of establishing large, well-annotated banks of RCC primary cultures for high-throughput drug screening in vitro and validation in vivo, providing a versatile platform together with xenografts and patient-derived precision-cut tissue slice tumorgrafts we developed previously for precilinical studies of RCC.

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