title: Development and characterization of clinically relevant tumor models from patients with renal cell carcinoma.
abstract: BACKGROUND
  Animal models are instrumental in understanding disease pathophysiology and mechanisms of therapy action and resistance in vivo.
  
  
  OBJECTIVE
  To establish and characterize a panel of mouse models of renal cell carcinoma (RCC) derived from patients undergoing radical nephrectomy.
  
  
  METHODS
  In vivo and in vitro animal experiments.
  
  
  METHODS
  Tumor tissues obtained during surgery were implanted into the subcutaneous space of female BALB/c nude mice and serially passaged into new mice. Tumors were characterized by histology, short tandem repeat (STR) fingerprinting, von Hippel-Lindau (VHL) gene sequencing, and single nucleotide polymorphism (SNP) analysis. Tumor-bearing mice were treated with sunitinib or everolimus. Primary cell cultures were derived from patient tumors and transfected with a lentivirus carrying the luciferase gene. Four subcutaneous xenograft mouse models were developed, representing papillary type 1, papillary type 2, clear cell, and clear cell with sarcomatoid features RCC.
  
  
  CONCLUSIONS
  RCC mouse models were established from four patients with distinct histologies of RCC. Tumor growth was dependent on histologic type, the size of the implanted tumor chip, and the passage number. Mouse tumors accurately represented their respective original patient tumors, as STR fingerprints were matching, histology was comparable, and SNP profiles and VHL mutation status were conserved with multiple passages. Bioluminescence imaging results were commensurate with subcutaneous xenograft growth patterns. Mice treated with sunitinib and everolimus exhibited an initial response, followed by a later stage of resistance to these agents, which mimics the clinical observations in patients with RCC.
  
  
  CONCLUSIONS
  We developed four mouse xenograft models of RCC with clear-cell and papillary histologies, with stable histologic and molecular characteristics. These models can be used to understand the basic biology of RCC as well as response and resistance to therapy.
authors.affiliation: Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Karam
authors.forename: Xiu-Ying
authors.initials: XY
authors.lastname: Zhang
authors.forename: Pheroze
authors.initials: P
authors.lastname: Tamboli
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: E Jason
authors.initials: EJ
authors.lastname: Abel
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Culp
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D016172:DNA Fingerprinting; D004195:Disease Models, Animal; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D020641:Polymorphism, Single Nucleotide; D011758:Pyrroles / Q000494:pharmacology; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D000077210:Sunitinib; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D006623:von Hippel-Lindau Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D007211:Indoles; D011758:Pyrroles; D000068338:Everolimus; D000077210:Sunitinib; D020123:Sirolimus