An orthotopic model of anaplastic thyroid carcinoma in athymic nude mice

An orthotopic model of anaplastic thyroid carcinoma in athymic nude mice
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DOI:
10.1158/1078-0432.ccr-04-1908
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发表时间:
2005-03-01
影响因子:
11.5
通讯作者:
Myers, JN
Myers, JN
中科院分区:
医学1区
文献类型:
--
作者:
Kim, S;Park, YW;Myers, JN

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目的:建立甲状腺间变性癌(anaplastic thyroid carcinoma,ATC)裸鼠原位模型,实验设计:将不同的甲状腺癌细胞系注射到裸鼠甲状腺内,以确定这种注射方法是否可行。然后将ATC细胞以各种浓度注射到裸鼠的甲状腺或皮下组织中,然后跟踪小鼠的肿瘤发展。肿瘤组织病理学检查局部浸润或区域或远处转移。结果:将肿瘤细胞注射到裸鼠甲状腺中在技术上是可行的,并导致甲状腺肿瘤的形成。ATC细胞系DRO在甲状腺中的致瘤性显著高于皮下组织。相反,口腔鳞状细胞癌细胞系TU 167在甲状腺中的致瘤性并不显著高于皮下组织。甲状腺中建立的ATC肿瘤也会产生食道和气管压迫的症状。喉和气管的局部侵犯以及肺转移率也很高。免疫组化染色显示较高的微血管密度,以及较高的表达血管内皮生长因子和白细胞介素-8在原位甲状腺肿瘤比异位tumor.Conclusion:原位模型ATC在无胸腺裸鼠的开发,密切概括了人类ATC的临床表现。该模型有助于理解ATC的发病机制,并有助于开发针对ATC的新疗法。
Purpose: To develop an orthotopic model of anaplastic thyroid carcinoma (ATC) in athymic nude mice.Experimental Design: Various thyroid carcinoma cell lines were injected into the thyroid gland of athymic nude mice to determine whether such injection was technically feasible. ATC cells were then injected into the thyroid gland or the subcutis of nude mice at various concentrations, and the mice were then followed for tumor development. The tumors were examined histopathologically for local invasion or regional or distant metastasis.Results: Injection of tumor cells into the thyroid glands of nude mice was technically feasible and resulted in the formation of thyroid tumors. The ATC cell line DRO showed significantly higher tumorigenicity in the thyroid gland than in the subcutis. In contrast, oral squamous cell carcinoma cell line TU167 shows no significantly higher tumorigenicity in the thyroid gland than in the subcutis. ATC tumors established in the thyroid gland also produced symptomatic compression of the esophagus and the trachea. Local invasion of the larynx and trachea was as well as high rates of pulmonary metastasis were also observed. Immunohistochemical staining showed higher microvessel density as well as higher expression of vascular endothelial growth factor and interleukin-8 in the orthotopic thyroid tumors than in ectopic tumors.Conclusion: An orthotopic model of ATC in athymic nude mice was developed that closely recapitulates the clinical findings of human ATC. This model should facilitate the understanding of the pathogenesis of ATC and aid in the development of novel therapies against ATC.