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. (Cancer Sci 2013; 104: 631-638)

Establishment and characterization of esophageal squamous cell carcinoma patient-derived xenograft mouse models for preclinical drug discovery

“…Our successful engraftment rate of 38.5% was in the range of engraftment rates observed in similar patient-derived xenograft mouse model studies. 28,[46][47][48][49] Correlative analysis between patient clinical characteristics and PDECX model establishment success rates demonstrated no statistically significant factors, but did, however, show potential negative trends associated with nerve invasion status and HER2 amplification or overexpression.…”

Clinical Outcomes of TP53 Mutations in Cancers

“…These patient-derived tumor xenografts (PDTXs) are currently a valuable resource for study (Tentler et al 2012) and increasingly performing as predictors of response to targeted therapy (Stewart et al 2015). Because TP53 is ubiquitously altered in cancers, TP53 mutations are a tool to confirm the provenance of PDTX (Park et al 2013;Walters et al 2013;Dodbiba et al 2015). Moreover, selection pressures that lead to expansion of aggressive clones on implantation of primary tumors appear to replicate metastatic colonization such that TP53 mutations found in PTDX can serve as a beacon to track the origin of metastases back to minor subclones present in the primary tumors (Bousquet et al 2015).…”

Patient-derived bladder cancer xenografts: a systematic review

“…29 In the 6 xenografts with 2 or more passages they found 2 completely identical STR profiles and 4 nearly identical profiles for all STR loci; 4 of 6 had identical mutations in the TP53, HRAS, BRAF, and CTNNB1 (catenin [cadherin-associated protein], beta 1) genes; and all 6 xenografts had genomic alterations similar to the original tumor samples.…”

“…However, some studies report the correlation between engraftment success and clinical prognosis or pathologic stage and grade of the original tumor. 24 Ki-67, CD56, synaptophysin Park et al (2013) 29 Mutations STR genotyping, array-comparative genomic hybridization Bernardo et al (2014) 25 P53, Ki-67, p63, ck20, sTn -sTn WB Abbreviations: CEA, carcinoembryonic antigen; EBV, Epstein-Barr virus; HCG, human chorionic gonadotropin; HLA-A, major histocompatibility complex, class I, A; HLA-ABC, human major histocompatibility complex, class I, HLA-A, B and C; LMP, latent membrane protein; PCNA, proliferating-cell nuclear antigen; PNA, Peanut agglutinin.…”