Establishment in severe combined immunodeficiency mice of subrenal capsule xenografts and transplantable tumor lines from a variety of primary human lung cancers: Potential models for studying tumor progression-related changes
Establishment in severe combined immunodeficiency mice of subrenal capsule xenografts and transplantable tumor lines from a variety of primary human lung cancers: Potential models for studying tumor progression-related changes
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DOI：
10.1158/1078-0432.ccr-06-0252
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发表时间：
2006-07-01
影响因子：
11.5
通讯作者：
Wang, Yu-Zhuo
中科院分区：
文献类型：
--
作者：
Cutz, Jean-Claude;Guan, Jun;Wang, Yu-Zhuo
目的：肺癌是一种生物多样性疾病，反映其多样性的相关模型将有助于改善现有的治疗方法。为了建立这样的模型，我们开发和评估异种移植的各种人类lung cancer.Experimental设计：使用非肥胖糖尿病/严重的联合免疫缺陷小鼠，肾包膜下异种移植产生的原发性肺癌组织，包括中度和低分化鳞状细胞癌，腺癌，腺鳞癌，小细胞癌，大细胞未分化癌，和癌肉瘤。4 ~ 12周后，收集异种移植物进行连续移植，并通过组织学、染色体和细胞遗传学分析与原始组织进行比较。H&E染色显示异种移植物保留了原始癌症的主要组织学特征。免疫组织化学和荧光原位杂交证实了肿瘤细胞的人类起源和小鼠支持性基质异种移植物的发展。从快速生长的肿瘤（>5代）开发了4个可移植系，即，小细胞肺癌、大细胞未分化癌、肺癌肉瘤和鳞状细胞癌。分析，包括光谱核型分析，比较基因组杂交，荧光原位杂交，发现异种移植物的遗传相似的原始肿瘤，显示染色体异常与核型变化报告为lung cancer.Conclusions：肾包膜下异种移植的方法基本上提供了一个活的肿瘤银行来自患者的材料和一种手段，用于分离和扩大特定的细胞群体。可移植的肿瘤细胞系似乎为研究肿瘤进展的各个方面提供了良好的模型，并为开发新的治疗方案提供了平台，并有可能为患者量身定制治疗方法。
Purpose: Lung cancer is a biologically diverse disease and relevant models reflecting its diversity would facilitate the improvement of existing therapies. With a view to establishing such models, we developed and evaluated xenografts of a variety of human lung cancers.Experimental Design: Using nonobese diabetic/severe combined immunodeficiency mice, subrenal capsule xenografts were generated from primary lung cancer tissue, including moderately and poorly differentiated squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, small cell carcinoma, large cell undifferentiated carcinoma, and carcinosarcoma. After 4 to 12 weeks, xenografts were harvested for serial transplantation and comparison with the original tissue via histologic, chromosomal, and cytogenetic analyses.Results: Xenografts were successfully established. H&E staining showed that xenografts retained major histologic features of the original cancers. Immunohistochemistry and fluorescence in situ hybridization confirmed the human origin of the tumor cells and development in xenografts of murine supportive stroma. Four transplantable lines were developed from rapidly growing tumors (>5 generations), i.e., a small cell lung carcinoma, large cell undifferentiated carcinoma, pulmonary carcinosarcoma, and squamous cell carcinoma. Analyses including spectral karyotyping, comparative genomic hybridization, and fluorescence in situ hybridization, revealed that the xenografts were genetically similar to the original tumors, showing chromosomal abnormalities consistent with karyotypic changes reported for lung cancer.Conclusions: The subrenal capsule xenograft approach essentially provides a living tumor bank derived from patient material and a means for isolating and expanding specific cell populations. The transplantable tumor lines seem to provide good models for studying various aspects of tumor progression and a platform for developing novel therapeutic regimens, with the possibility of patient-tailored therapies.