Establishment of two ovarian cancer orthotopic xenograft mouse models for in vivo imaging: A comparative study
Establishment of two ovarian cancer orthotopic xenograft mouse models for in vivo imaging: A comparative study
复制标题
两种卵巢癌原位异种移植小鼠体内成像模型的建立：比较研究
DOI：
10.3892/ijo.2017.4115
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发表时间：
2017-10-01
影响因子：
5.2
通讯作者：
Wang, Zehua
中科院分区：
文献类型：
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作者：
Guo, Jing;Cai, Jing;Wang, Zehua
原位肿瘤动物模型是新型治疗干预措施临床前研究的最佳选择。本研究的目的是比较两种类型的卵巢癌原位异种移植（OCOX）小鼠模型，即细胞原位注射（COI）和手术原位植入（SOI），关于异种移植形成率、体内成像、肿瘤生长和转移以及肿瘤微环境。通过体内生物发光成像监测肿瘤的形成和进展。分别通过 EdU 和划痕实验检测细胞增殖和迁移能力。采用免疫组化法检测肿瘤样本中α-SMA、CD34、MMP2、MMP9、vimentin、E-cadherin、Ki67的表达。结果，我们利用卵巢癌细胞系ES2和SKOV3成功建立了COI-和SOI-OCOX小鼠模型。 COI和SOI模型中的肿瘤形成率分别为87.5%和100%。 37.5% 的 COI 模型疑似发生肿瘤细胞渗漏。 SOI异种移植物比COI异种移植物生长更快，原发肿瘤更大，并且转移性更强。产生 SOI 异种移植物的细胞的迁移和增殖特性明显比体外衍生 COI 异种移植物的细胞更明显。 SOI异种移植物中的肿瘤细胞表现出间充质表型，并且比COI异种移植物中的肿瘤细胞增殖更活跃。此外，与COI肿瘤相比，SOI肿瘤含有更多的癌症相关成纤维细胞、基质金属肽酶2和9。总之，SOI是建立模仿卵巢癌生长和转移临床过程的OCOX小鼠模型的可行且可靠的技术，尽管SOI比COI在技术上更加困难和耗时。
Orthotopic tumor animal models are optimal for preclinical research of novel therapeutic interventions. The aim of the present study was to compare two types of ovarian cancer orthotopic xenograft (OCOX) mouse models, i.e. cellular orthotopic injection (COI) and surgical orthotopic implantation (SOI), regarding xenograft formation rate, in vivo imaging, tumor growth and metastasis, and tumor microenvironment. The tumor formation and progression were monitored by bioluminescent in vivo imaging. Cell proliferation and migration abilities were detected by EdU and scratch assays, respectively. Expression of alpha-SMA, CD34, MMP2, MMP9, vimentin, E-cadherin and Ki67 in tumor samples were detected by immunohistochemistry. As a result, we successfully established COI- and SOI-OCOX mouse models using ovarian cancer cell lines ES2 and SKOV3. The tumor formation rate in the COI and SOI models were 87.5 and 100%, respectively. Suspected tumor cell leakage occurred in 37.5% of the COI models. The SOI xenografts grew faster, held larger primary tumors, and were more metastatic than the COI xenografts. The migration and proliferation properties of the cells that generated SOI xenografts were significantly starker than those deriving COI xenografts in vitro. The tumor cells in SOI xenografts exhibited a mesenchymal phenotype and proliferated more actively than those in the COI xenografts. Additionally, compared with the COI tumors, the SOI tumors contained more cancer associated fibroblasts, matrix metallopeptidase 2 and 9. In conclusion, SOI is a feasible and reliable technique to establish OCOX mouse models mimicking the clinical process of ovarian cancer growth and metastasis, although SOI is more technically difficult and time-consuming than COI.