Colorectal cancer patient-derived xenografted tumors maintain characteristic features of the original tumors
Colorectal cancer patient-derived xenografted tumors maintain characteristic features of the original tumors
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DOI：
10.1016/j.jss.2013.11.010
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发表时间：
2014-04-01
影响因子：
2.2
通讯作者：
Lee, Woo Yong
中科院分区：
文献类型：
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作者：
Cho, Yong Beom;Hong, Hye Kyung;Lee, Woo Yong
背景：尽管过去几十年结肠癌的结果有了显着改善，但更有效的治疗策略的临床前开发仍然受到临床相关动物模型可用性的限制。为了满足这些临床未满足的需求，我们利用新鲜的手术样本建立了一个特征良好的结直肠癌体内临床前平台。方法：将手术中产生的原发性和转移性结直肠肿瘤组织（1·2mm（3））植入裸鼠皮下空间并在体内连续传代。采用突变状态、苏木精和伊红染色、短串联重复分析和阵列比较基因组杂交来验证患者肿瘤与异种移植瘤之间分子特征的相似性。结果：从143例患者的手术标本中获得97个免疫缺陷小鼠异种移植模型（建立率67%）。 39 个异种移植模型在小鼠中进一步连续扩增，达到 1000-1500 mm(3) 大小的平均时间为 90 +/- 20 天。组织学和免疫组织化学分析揭示了患者和异种移植肿瘤之间高度的病理相似性，包括组织学结构以及 CEA、CK7 和 CD20 的表达。分子分析表明，每个患者肿瘤的基因突变、基因组改变和基因表达模式在相应的异种移植肿瘤中也得到了很好的保存。结论：源自新鲜手术样本的异种移植动物模型保留了原始肿瘤的关键特征，表明该体内平台可用于结直肠癌新治疗方法的临床前开发。 (c) 2014 Elsevier Inc. 保留所有权利。
Background: Despite significant improvements in colon cancer outcomes over the past few decades, preclinical development of more effective therapeutic strategies is still limited by the availability of clinically relevant animal models. To meet those clinical unmet needs, we generated a well-characterized in vivo preclinical platform for colorectal cancer using fresh surgical samples.Methods: Primary and metastatic colorectal tumor tissues ( 1 2 mm(3)) that originate from surgery were implanted into the subcutaneous space of nude mice and serially passaged in vivo. Mutation status, hematoxylin and eosin staining, short tandem repeat profiling, and array comparative genomic hybridization were used to validate the similarity of molecular characteristics between the patient tumors and tumors obtained from xenografts.Results: From surgical specimens of 143 patients, 97 xenograft models were obtained in immunodeficient mice (establish rate 67%). Thirty-nine xenograft models were serially expanded further in mice with a mean time to reach a size of 1000-1500 mm(3) of 90 +/- 20 d. Histologic and immunohistochemical analyses revealed a high degree of pathologic similarity including histologic architecture and expression of CEA, CK7, and CD20 between the patient and xenograft tumors. Molecular analysis showed that genetic mutations, genomic alterations, and gene expression patterns of each patient tumor were also well conserved in the corresponding xenograft tumor.Conclusions: Xenograft animalmodels derived from fresh surgical samplemaintained the key characteristic features of the original tumors, suggesting that this in vivo platform can be useful for preclinical development of novel therapeutic approaches to colorectal cancers. (c) 2014 Elsevier Inc. All rights reserved.