Establishment and characterization of human urothelial cancer xenografts in severe combined immunodeficient mice.
OBJECTIVE
To establish and characterize a murine xenograft model of human urothelial cancer in severe combined immunodeficient (SCID) mice for therapeutic simulation.


METHODS
Pieces of 30 freshly resected urothelial tumors (24 obtained from bladder and 6 from ureter or pelvis) were implanted subcutaneously into SCID mice, and xenograft tumors were passed in tumorigenic cases. At each passage, histopathology, TP53 mutational status assessed by yeast p53 functional assay, and the Ki-67 labeling index (LI) were examined to evaluate the preservation of original features. A growth delay assay after single-dose irradiation was performed in four representative xenografts.


RESULTS
Tumor growth was observed in 18 mice (60%, 18/30). Histologically, 15 of the 18 were epithelial carcinomas similar to the original tumors, whereas the other 3 were Epstein-Barr virus-associated lymphoproliferative disease, resulting in a 50% (15/30) take rate. No correlation was found between the tumor take rate and the clinicopathologic features, TP53 mutational status, or Ki-67 LI of the patients' tumors. Of these 15 xenografts, 11 xenografts were passed from 3 to 10 generations. TP53 mutational status remained stable during the passages, and the Ki-67 LI of eight xenografts was within a range of 50% of the LI of the original tumors, although the other three xenografts increased by over 50%. Specific growth delay after irradiation, independent of the original tumor growth speed and Ki-67 LI, was observed in four xenografts.


CONCLUSIONS
SCID mice are useful recipients for investigations of human urothelial cancer with a wide biological range. This easy-to-handle xenograft system can help to develop a better in vivo preclinical evaluation system for therapeutic agents as well as the investigation of tumor pathophysiology.
Abe
Takashige
T
Department of Urology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. takataka@rf6.so-net.ne.jp
Tada
Mitsuhiro
M
Shinohara
Nobuo
N
Okada
Futoshi
F
Itoh
Tomoo
T
Hamada
Jun-Ichi
J
Harabayashi
Toru
T
Chen
Qinzhong
Q
Moriuchi
Tetsuya
T
Nonomura
Katsuya
K
D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D014516:Ureteral Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*
D019394:Ki-67 Antigen; D012334:RNA, Neoplasm