Oncotarget

Research Papers:

Establishment of a large panel of patient-derived preclinical models of human renal cell carcinoma

Hervé Lang, Claire Béraud, Audrey Bethry, Sabrina Danilin, Véronique Lindner, Catherine Coquard, Sylvie Rothhut and Thierry Massfelder _

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Oncotarget. 2016; 7:59336-59359. https://doi.org/10.18632/oncotarget.10659

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Abstract

Hervé Lang1, Claire Béraud2, Audrey Bethry2, Sabrina Danilin3, Véronique Lindner4, Catherine Coquard3, Sylvie Rothhut3, Thierry Massfelder3

1Department of Urology, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Strasbourg, 67091 France

2UROLEAD SAS, School of Medicine, Strasbourg, 67085 France

3INSERM U1113, Section of Cell Signalisation and Communication in Kidney and Prostate Cancer, University of Strasbourg, School of Medicine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, 67085 France

4Department of Pathology, Hôpitaux Universitaires de Strasbourg, Hôpital de Strasbourg-Hautepierre, Strasbourg, 67200 France

Correspondence to:

Thierry Massfelder, email: massfeld@unistra.fr

Keywords: renal cell carcinoma, human tumors, patient-derived xenograft models

Abbreviations: CCC, clear cell renal cell carcinoma; PDX, patient-derived tumor xenograft; VHL, von Hippel-Lindau tumor suppressor gene

Received: September 08, 2015     Accepted: July 05, 2016     Published: July 18, 2016

ABSTRACT

The objective of the present work was to establish a large panel of preclinical models of human renal cell carcinoma (RCC) directly from patients, faithfully reproducing the biological features of the original tumor. RCC tissues (all stages/subtypes) were collected for 8 years from 336 patients undergoing surgery, xenografted subcutaneously in nude mice, and serially passaged into new mice up to 13 passages. Tissue samples from the primary tumor and tumors grown in mice through passages were analyzed for biological tissue stability by histopathology, mRNA profiling, von Hippel-Lindau gene sequencing, STR fingerprinting, growth characteristics and response to current therapies. Metastatic models were also established by orthotopic implantation and analyzed by imagery. We established a large panel of 30 RCC models (passage > 3, 8.9% success rate). High tumor take rate was associated with high stage and grade. Histopathologic, molecular and genetic characteristics were preserved between original tumors and case-matched xenografts. The models reproduced the sensitivity to targeted therapies observed in the clinic. Overall, these models constitute an invaluable tool for the clinical design of efficient therapies, the identification of predictive biomarkers and translational research.


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