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 6 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: (1) histologic examination, (2) short tandem repeat (STR) genotyping, (3) mutational analysis, and (4) 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 6 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, 4 out of 6 xenografts had mutations identical to the original samples for TP53, HRAS, BRAF, and CTNNB1. Array-CGH analysis revealed that all 6 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.
Written by:
Park B, Jeong BC, Choi YL, Kwon GY, Lim JE, Seo SI, Jeon SS, Lee HM, Choi HY, Lee KS. Are you the author?
Departments of Urology, Sungkyunkwan University School of Medicine, Seoul, Korea; Departments of Institute for Refractory Cancer Research, Sungkyunkwan University School of Medicine, Seoul, Korea; Department of Urology, Kangnam General Hospital, Yongin, Korea.
Reference: Cancer Sci. 2013 Feb 6. Epub ahead of print.
doi: 10.1111/cas.12123
PubMed Abstract
PMID: 23384396
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