Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University, School of Medicine, China.
Oral Oncol. 2013 Jun;49(6):542-50. doi: 10.1016/j.oraloncology.2013.01.002. Epub 2013 Feb 9.
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.
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.
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.
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.
膜联蛋白 A1 在肿瘤发生中的功能作用还不太清楚。本研究旨在调查 Annexin A1 蛋白表达与 232 例口腔鳞状细胞癌(OSCC)患者活检样本的病理分化程度之间的关系;并评估 Annexin A1 对 OSCC 细胞增殖和肿瘤发生的潜在作用。
我们通过免疫组织化学染色研究了 Annexin A1 表达与 232 例 OSCC 患者活检样本的病理分化程度之间的关系,以及 Annexin A1 表达与体外和体内 OSCC 模型中的细胞增殖和肿瘤形成之间的关系。
Annexin A1 的表达与 OSCC 患者的病理分化程度显著相关,较低的 Annexin A1 表达与较差的分化程度相关。在 OSCC 细胞系 CAL27 和 Tca8113 中强制过表达 Annexin A1 显著降低了细胞增殖,而下调 OSCC 细胞系 HB96 中的 Annexin A1 表达则显著增加了 HB96 细胞的增殖。在裸鼠中,CAL27 细胞过表达 Annexin A1 形成的肿瘤生长明显慢于亲本 CAL27 细胞,且核 Ki-67 标记指数明显降低。有趣的是,这些肿瘤还表现出良好的分化组织学模式,而来自亲本细胞的肿瘤则始终呈中度分化。
这些数据支持 Annexin A1 表达与病理分化程度之间存在显著相关性,以及 Annexin A1 在抑制 OSCC 细胞增殖和细胞分化方面的功能作用。