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CD44+癌细胞诱导的转移:一种可行的颈部转移模型。

CD44+ cancer cell-induced metastasis: A feasible neck metastasis model.

作者信息

Wu Tian-Fu, Chen Lei, Bu Lin-Lin, Gao Jie, Zhang Wen-Feng, Jia Jun

机构信息

The State Key Laboratory Breeding Base of Basic Science of Stomatology, Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China; Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.

The State Key Laboratory Breeding Base of Basic Science of Stomatology, Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.

出版信息

Eur J Pharm Sci. 2017 Apr 1;101:243-250. doi: 10.1016/j.ejps.2017.02.020. Epub 2017 Feb 13.

Abstract

Neck metastasis of oral squamous cell carcinoma (OSCC) indicates a poor prognosis. Few neck metastasis models are currently available for drug trials and clinical research on OSCC. This study constructed a feasible animal model of neck metastasis by using CD44+ stem cell-like cancer cells. Real-time PCR was used to determine the expression levels of several reported cancer stem cell (CSC) markers, including CD44, CD133, ALDH1 and OCT4, in three OSCC cell lines. Magnetic sorting and DiO/DiD labelling were used to isolate subpopulations of cells and monitor cancer cell migration. Sorted and labelled CSC-like cells were injected into the tongue of nude mice. Tumour and metastatic lymph nodes were histologically examined through immunostaining and tracer staining. High rate of metastasis was observed in neck lymph nodes in CD44+ group. This phenomenon was confirmed in clinical OSCC patients, and CD44 expression levels were higher in tumours with lymph node metastasis than in carcinomas in situ. Therefore, we have successfully constructed a neck metastasis model by using CD44+ CSCs. This model can form tumour and show metastases within a short period of time compared with other models; additionally, this model may be used in short-term pharmacological experiments involving animals and in basic clinical studies.

摘要

口腔鳞状细胞癌(OSCC)的颈部转移提示预后不良。目前用于OSCC药物试验和临床研究的颈部转移模型很少。本研究利用CD44 + 干细胞样癌细胞构建了一种可行的颈部转移动物模型。采用实时PCR检测三种OSCC细胞系中几种已报道的癌症干细胞(CSC)标志物的表达水平,包括CD44、CD133、醛脱氢酶1(ALDH1)和八聚体结合转录因子4(OCT4)。利用磁性分选和DiO/DiD标记来分离细胞亚群并监测癌细胞迁移。将分选并标记的CSC样细胞注射到裸鼠舌部。通过免疫染色和示踪染色对肿瘤和转移淋巴结进行组织学检查。在CD44 + 组的颈部淋巴结中观察到高转移率。这一现象在临床OSCC患者中得到证实,且有淋巴结转移的肿瘤中CD44表达水平高于原位癌。因此,我们成功利用CD44 + CSCs构建了颈部转移模型。与其他模型相比,该模型可在短时间内形成肿瘤并出现转移;此外,该模型可用于涉及动物的短期药理学实验和基础临床研究。

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