title: Development and characterization of a bladder cancer xenograft model using patient-derived tumor tissue.
abstract: Most of the cancer xenograft models are derived from tumor cell lines, but they do not sufficiently represent clinical cancer characteristics. Our objective was to develop xenograft models of bladder cancer derived from human tumor tissue and characterize them molecularly as well as histologically. A total of 65 bladder cancer tissues were transplanted to immunodeficient mice. Passagable six cases with clinico-pathologically heterogeneous bladder cancer were selected and their tumor tissues were collected (012T, 025T, 033T, 043T, 048T, and 052T). Xenografts were removed and processed for the following analyses: (i) histologic examination, (ii) short tandem repeat (STR) genotyping, (iii) mutational analysis, and (iv) array-based comparative genomic hybridization (array-CGH). The original tumor tissues (P 0) and xenografts of passage 2 or higher (≥P2) were analyzed and compared. As a result, hematoxylin and eosin staining revealed the same histologic architecture and degree of differentiation in the primary and xenograft tumors in all six cases. Xenograft models 043T_P2 and 048T_P2 had completely identical STR profiles to the original samples for all STR loci. The other models had nearly identical STR profiles. On mutational analysis, four out of six xenografts had mutations identical to the original samples for TP53, HRAS, BRAF, and CTNNB1. Array-CGH analysis revealed that all six xenograft models had genomic alterations similar to the original tumor samples. In conclusion, our xenograft bladder cancer model derived from patient tumor tissue is expected to be useful for studying the heterogeneity of the tumor populations in bladder cancer and for evaluating new treatments.
authors: Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Bumsoo
authors: B
authors: Park
authors: Byong Chang
authors: BC
authors: Jeong
authors: Yoon-La
authors: YL
authors: Choi
authors: Ghee Young
authors: GY
authors: Kwon
authors: Joung Eun
authors: JE
authors: Lim
authors: Seong Il
authors: SI
authors: Seo
authors: Seong Soo
authors: SS
authors: Jeon
authors: Hyun Moo
authors: HM
authors: Lee
authors: Han Yong
authors: HY
authors: Choi
authors: Kyu-Sung
authors: KS
authors: Lee
mesh_terms: D000368:Aged; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
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