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胰岛素样生长因子结合蛋白3(IGFBP3)的过表达与鼻咽癌的不良预后和肿瘤转移相关。

Overexpression of IGFBP3 is associated with poor prognosis and tumor metastasis in nasopharyngeal carcinoma.

作者信息

Bao Lili, Liu Hao, You Bo, Gu Miao, Shi Si, Shan Ying, Li Li, Chen Jing, You Yiwen

机构信息

Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226000, China.

出版信息

Tumour Biol. 2016 Nov;37(11):15043-15052. doi: 10.1007/s13277-016-5400-8. Epub 2016 Sep 22.

Abstract

Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. However, the role of IGFBP3 in tumor metastasis remains under debate. Nasopharyngeal carcinoma (NPC) is a highly metastatic head and neck cancer. And it fails to achieve the desired therapeutic efficacy in patients with metastasis, while the role of IGFBP3 in NPC is still unclear. In this study, we first used immunohistochemistry to explore the expression of IGFBP3 in NPC tissues. We found that IGFBP3 was significantly elevated in NPC and its expression level was correlated with N classification, distant metastasis, and TNM clinical stage (all P < 0.05). Patients with high expression of IGFBP3 had poorer survival rate (P < 0.05). In addition, we found that downregulation of IGFBP3 inhibited cell migration and adhesion by Transwell migration assay, wounding healing assay, and cell adhesion assays in vitro. Besides, NPC cells stimulated with recombinant IGFBP3 accelerated migration and adhesion. These data suggest overexpression of IGFBP3 promotes tumor metastasis in NPC, which makes it a potential therapeutic target.

摘要

胰岛素样生长因子结合蛋白3(IGFBP3)是一种N-连接糖基化、磷酸化的蛋白质,据报道它可调节癌症的进展和转移。然而,IGFBP3在肿瘤转移中的作用仍存在争议。鼻咽癌(NPC)是一种具有高度转移性的头颈癌。对于发生转移的患者,其治疗效果未能达到预期,而IGFBP3在鼻咽癌中的作用仍不清楚。在本研究中,我们首先采用免疫组织化学方法探究IGFBP3在鼻咽癌组织中的表达情况。我们发现,IGFBP3在鼻咽癌中显著升高,其表达水平与N分级、远处转移及TNM临床分期均相关(均P<0.05)。IGFBP3高表达的患者生存率较低(P<0.05)。此外,我们通过体外Transwell迁移实验、划痕愈合实验及细胞黏附实验发现,IGFBP3的下调抑制了细胞迁移和黏附。此外,用重组IGFBP3刺激鼻咽癌细胞可加速其迁移和黏附。这些数据表明,IGFBP3的过表达促进了鼻咽癌的肿瘤转移,这使其成为一个潜在的治疗靶点。

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