Development and characterization of a bladder cancer xenograft model using patient-derived tumor tissue
Development and characterization of a bladder cancer xenograft model using patient-derived tumor tissue
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DOI：
10.1111/cas.12123
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发表时间：
2013-05-01
期刊：
影响因子：
5.7
通讯作者：
Lee, Kyu-Sung
中科院分区：
文献类型：
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作者：
Park, Bumsoo;Jeong, Byong Chang;Lee, Kyu-Sung
大多数癌症异种移植模型来源于肿瘤细胞系，但它们不足以代表临床癌症特征。我们的目标是开发来自人类肿瘤组织的膀胱癌异种移植模型，并从分子和组织学上对其进行表征。共65个膀胱癌组织移植到免疫缺陷小鼠。选择临床病理特征不均一的膀胱癌患者6例，分别收集其肿瘤组织（012 T、025 T、033 T、043 T、048 T、052 T）。取出异种移植物并进行以下分析：（i）组织学检查，（ii）短串联重复序列（STR）基因分型，（iii）突变分析，和（iv）基于阵列的比较基因组杂交（阵列-CGH）。分析并比较原始肿瘤组织（P0）和第2代或更高代（P2）的异种移植物。结果，苏木精和伊红染色显示所有6例原发性和异种移植瘤的组织学结构和分化程度相同。异种移植物模型043T_P2和048T_P2对于所有STR基因座具有与原始样品完全相同的STR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个具有与原始样品相同的TP 53、HRAS、BRAF和CTNNB 1突变。阵列-CGH分析显示，所有六种异种移植模型具有与原始肿瘤样品相似的基因组改变。总之，我们的来自患者肿瘤组织的异种移植膀胱癌模型预计可用于研究膀胱癌中肿瘤群体的异质性和评估新的治疗方法。
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.