Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Cancer Sci. 2013 May;104(5):631-8. doi: 10.1111/cas.12123. Epub 2013 Mar 24.
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.
大多数癌症异种移植模型都是源自肿瘤细胞系，但它们并不能充分代表临床癌症特征。我们的目标是开发源自人肿瘤组织的膀胱癌异种移植模型，并对其进行分子和组织学特征分析。共将 65 份膀胱癌组织移植到免疫缺陷小鼠中。选择了 6 例具有临床病理异质性的可传代膀胱癌，并收集了其肿瘤组织（012T、025T、033T、043T、048T 和 052T）。移除异种移植物并进行以下分析：（i）组织学检查，（ii）短串联重复（STR）基因分型，（iii）突变分析和（iv）基于阵列的比较基因组杂交（array-CGH）。分析了原始肿瘤组织（P0）和传代 2 或更高代（≥P2）的异种移植物，并进行了比较。结果，苏木精和伊红染色显示在所有 6 例中，原发肿瘤和异种移植物具有相同的组织学结构和分化程度。异种移植物模型 043T_P2 和 048T_P2 在所有 STR 位点上与原始样本具有完全相同的 STR 图谱。其他模型具有几乎相同的 STR 图谱。在突变分析中，6 个异种移植物中有 4 个具有与原始样本相同的 TP53、HRAS、BRAF 和 CTNNB1 突变。array-CGH 分析显示，所有 6 个异种移植模型都具有与原始肿瘤样本相似的基因组改变。总之，我们从患者肿瘤组织中获得的膀胱癌异种移植模型有望用于研究膀胱癌肿瘤群体的异质性，并评估新的治疗方法。
