title: Establishment of a large panel of patient-derived preclinical models of human renal cell carcinoma.
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.
authors.affiliation: Department of Urology, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Strasbourg, 67091 France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Lang
authors.affiliation: UROLEAD SAS, School of Medicine, Strasbourg, 67085 France.
authors.forename: Claire
authors.initials: C
authors.lastname: Béraud
authors.affiliation: UROLEAD SAS, School of Medicine, Strasbourg, 67085 France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Bethry
authors.affiliation: INSERM 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.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Danilin
authors.affiliation: Department of Pathology, Hôpitaux Universitaires de Strasbourg, Hôpital de Strasbourg-Hautepierre, Strasbourg, 67200 France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Lindner
authors.affiliation: INSERM 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.
authors.forename: Catherine
authors.initials: C
authors.lastname: Coquard
authors.affiliation: INSERM 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.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rothhut
authors.affiliation: INSERM 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.
authors.forename: Thierry
authors.initials: T
authors.lastname: Massfelder
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D023041:Xenograft Model Antitumor Assays
keywords: human tumors; patient-derived xenograft models; renal cell carcinoma