TY - JOUR
T1 - Development and characterization of clinically relevant tumor models from patients with renal cell carcinoma
AU - Karam, Jose A.
AU - Zhang, Xiu Ying
AU - Tamboli, Pheroze
AU - Margulis, Vitaly
AU - Wang, Hua
AU - Abel, E. Jason
AU - Culp, Stephen H.
AU - Wood, Christopher G.
N1 - Funding Information:
Acknowledgment statement: The authors acknowledge the T. C. Hsu Molecular Cytogenetics Core, Characterized Cell Line Core, and the DNA Analysis Facilities at The University of Texas MD Anderson Cancer Center (under Cancer Center Support Grant NCI CA016672).
PY - 2011/4
Y1 - 2011/4
N2 - 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. Design, setting, and participants: In vivo and in vitro animal experiments. Measurements: 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. Results and limitations: 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.
AB - 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. Design, setting, and participants: In vivo and in vitro animal experiments. Measurements: 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. Results and limitations: 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.
KW - Mouse model
KW - Renal cell carcinoma
KW - Xenograft
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U2 - 10.1016/j.eururo.2010.11.043
DO - 10.1016/j.eururo.2010.11.043
M3 - Article
C2 - 21167632
AN - SCOPUS:79952280562
SN - 0302-2838
VL - 59
SP - 619
EP - 628
JO - European urology
JF - European urology
IS - 4
ER -