Cell Line Derived Xenograft Mouse Models Are a Suitable in vivo Mode for Studying Tumor Budding in Colorectal Cancer
Cell Line Derived Xenograft Mouse Models Are a Suitable in vivo Mode for Studying Tumor Budding in Colorectal Cancer
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DOI：
10.3389/fmed.2019.00139
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发表时间：
2019-06-27
影响因子：
3.9
通讯作者：
Zlobec, Inti
中科院分区：
文献类型：
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作者：
Georges, Laurent M. C.;De Wever, Olivier;Zlobec, Inti
肿瘤出芽（TB）是结直肠癌（CRC）重要的预后指标，并与转移有关。然而，结核病的机制尚未完全阐明，一个主要的限制是缺乏体内模型。在这里，我们确定了人类细胞系衍生的异种移植物（CDX）作为结直肠癌中结核模型的适用性。对两种CDX模型（HT-29, n = 12, HCT-8, n = 8）和人CRC （n = 27个高级别和25个低级别出芽肿瘤）的泛细胞角蛋白（CK）染色的下一代组织微阵列（ngTMA）进行TB评估。进行E-cadherin、β -catenin、Ki-67、ZEB1和TWIST1的免疫组织化学检测。HT-29和HCT-8分别主要为高级别和无/低级别结核肿瘤。HT-29 CDX肿瘤中心（瘤内萌芽，ITB）的TB计数明显高于人类CRC （p = 0.0099）。浸润前结核计数无差异（瘤周出芽，PTB; p = 0.07）。在CDX和人CRC中，ITB和PTB有很强的相关性（r = 0.438和r = 0.62）。CDX和人类CRC组织的免疫组织化学特征是相似的。CDX小鼠模型中的结核在表型上与人类crc相似，并突出了可比较的蛋白质谱。HT-29 CDX可作为TB体内评价的合适模型。
Tumor budding (TB) is an important prognostic parameter in colorectal cancer (CRC) and associated with metastasis. However, the mechanisms of TB have not been fully elucidated and a major limitation is the absence of in vivo models. Here, we determine the suitability of human cell line derived xenografts (CDX) as models of TB in CRC. Pan-cytokeratin (CK)-stained next-generation Tissue Microarrays (ngTMA) of two CDX models (HT-29, n = 12 and HCT-8, n = 8) and human CRC (n = 27 high-grade and 25 low-grade budding tumors, each) were evaluated for TB. lmmunohistochemistry for E-cadherin, beta-catenin, Ki-67, ZEB1, and TWIST1 was performed. HT-29 and HCT-8 were predominantly high-grade and no/low-grade TB tumors, respectively. TB counts in the tumor center (intratumoral budding, ITB) were significantly higher in HT-29 CDX tumors compared to human CRC (p = 0.0099). No difference was found in TB counts at the invasion front (peritumoral budding, PTB; p = 0.07). ITB and PTB were strongly correlated (r = 0.438 and r = 0.62 in CDX and human CRC, respectively). lmmunohistochemistry profiles were comparable in CDX and human CRC tissues. TB in the CDX mouse models is phenotypically similar to human CRCs and highlights comparable protein profiles. The HT-29 CDX could be a suitable model for the in vivo assessment of TB.