Annexin A1 down-regulation in oral squamous cell carcinoma correlates to pathological differentiation grade
Annexin A1 down-regulation in oral squamous cell carcinoma correlates to pathological differentiation grade
复制标题
口腔鳞状细胞癌中膜联蛋白 A1 的下调与病理分化级别相关
DOI：
10.1016/j.oraloncology.2013.01.002
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发表时间：
2013-06-01
期刊：
影响因子：
4.8
通讯作者：
Zhong, Lai-ping
中科院分区：
文献类型：
--
作者：
Zhu, Dong-wang;Yang, Xiao;Zhong, Lai-ping
目的：膜联蛋白A1在肿瘤发生中的功能作用尚不清楚。本研究的目的是研究一大批口腔鳞状细胞癌（OSCC）患者活检样本中膜联蛋白A1表达与病理分化等级之间的关系；并评价膜联蛋白A1在OSCC细胞增殖和肿瘤发生中的潜在作用。材料与方法：通过免疫组化染色研究232例OSCC患者活检标本中Annexin A1表达与病理分化等级的关系，以及体外和体内OSCC模型中Annexin A1表达与细胞增殖及肿瘤形成的关系。结果：在OSCC患者中，膜联蛋白A1表达与病理分化等级显著相关，膜联蛋白A1表达越低，分化等级越差。在OSCC细胞系CAL27和Tca8113中强制过表达Annexin A1可显著降低细胞增殖，而在OSCC细胞系HB96中下调Annexin A1表达可显著提高HB96细胞的增殖能力。与亲代CAL27细胞相比，过表达Annexin A1的CAL27细胞形成的肿瘤在裸鼠体内的生长速度明显减慢，核Ki-67标记指数明显降低。有趣的是，这些肿瘤也显示出良好分化的组织学模式，而由亲代细胞形成的肿瘤始终是中等分化的。结论：这些数据支持了膜联蛋白A1表达与病理分化程度的显著相关性，以及膜联蛋白A1在OSCC中抑制细胞增殖和细胞分化的功能作用。(C) 2013 Elsevier Ltd.版权所有。
Objectives: Functional role of Annexin A1 in tumorigenesis is poorly understood. The aim of this study was to investigate the relationship between Annexin A1 protein expression and pathological differentiation grade in biopsy samples from a large cohort of patients with oral squamous cell carcinoma (OSCC); and to evaluate the potential role of Annexin A1 on cell proliferation and tumorigenesis of OSCC.Materials and methods: We investigated the relationship between Annexin A1 expression by immunohistochemical staining and pathological differentiation grade of biopsy samples from 232 OSCC patients, and the relationship between Annexin A1 expression and cell proliferation as well as tumor formation using both in vitro and in vivo OSCC models.Results: Annexin A1 expression correlated significantly with pathological differentiation grade in OSCC patients, a lower Annexin A1 expression correlating with a poorer differentiation grade. Forced Annexin A1 overexpression in OSCC cell lines, CAL27 and Tca8113, significantly reduced the cell proliferation whereas down-regulation of Annexin A1 expression in OSCC cell line, HB96, significantly increased proliferation of HB96 cells. Tumors formed from CAL27 cells overexpressing Annexin A1 grown significantly slower compared to the parental CAL27 cells in nude mice and showed a significantly reduced nuclear Ki-67 labeling index. Interestingly, these tumors also showed a well differentiated histology pattern whereas the tumors formed from the parental cells were consistently moderately differentiated.Conclusions: These data support a significant correlation between Annexin A1 expression and pathological differentiation grade, and a functional role of Annexin A1 in inhibiting cell proliferation and cell differentiation in OSCC. (C) 2013 Elsevier Ltd. All rights reserved.