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膜金属蛋白酶 10 的过表达促进下咽鳞癌的肿瘤增殖、迁移和不良预后。

Overexpression of A disintegrin and metalloprotease 10 promotes tumor proliferation, migration and poor prognosis in hypopharyngeal squamous cell carcinoma.

机构信息

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

出版信息

Oncol Rep. 2017 Aug;38(2):866-874. doi: 10.3892/or.2017.5761. Epub 2017 Jun 27.

DOI:10.3892/or.2017.5761
PMID:28656294
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5562066/
Abstract

The aim of this study was to determine the effect of A disintegrin and metalloprotease 10 (ADAM10) protein expression on the progression, migration and prognosis of hypopharyngeal squamous cell carcinoma (HSCC). Immunohistochemistry and western blot analysis were performed to detect ADAM10 expression in human HSCC specimens. Cell Counting Kit-8 (CCK-8) assay, flow cytometry analysis and wound-healing assay were employed to investigate the effects of ADAM10 knockdown (ADAM10-RNAi) on major oncogenic properties of FaDu cells. We detected that ADAM10 was overexpressed in HSCC specimens and its expression level was associated with differentiation (p<0.001), tumor size (p=0.019), lymph node metastasis (p=0.001), clinical stage (p<0.001), proliferation marker Ki-67 expression (P=0.001) and overall survival (p<0.046). ADAM10-RNAi in FaDu cells resulted in the inhibition of proliferation and the decrease in migration. Moreover, mechanistic experiments revealed that ADAM10-RNAi resulted in an increase in E-cadherin and a decrease in N-cadherin and vimentin expression. Our study implies that high expression of ADAM10 promotes the proliferation and migration of HSCC. These findings may help to provide a method for treatment of HSCC.

摘要

本研究旨在探讨解整合素金属蛋白酶 10(ADAM10)蛋白表达对下咽鳞癌(HSCC)进展、迁移和预后的影响。采用免疫组织化学和 Western blot 分析检测人 HSCC 标本中 ADAM10 的表达。采用细胞计数试剂盒-8(CCK-8)检测、流式细胞术分析和划痕愈合试验研究 ADAM10 敲低(ADAM10-RNAi)对 FaDu 细胞主要致癌特性的影响。我们发现 ADAM10 在 HSCC 标本中过度表达,其表达水平与分化(p<0.001)、肿瘤大小(p=0.019)、淋巴结转移(p=0.001)、临床分期(p<0.001)、增殖标志物 Ki-67 表达(P=0.001)和总生存(p<0.046)有关。ADAM10-RNAi 在 FaDu 细胞中导致增殖抑制和迁移减少。此外,机制实验表明,ADAM10-RNAi 导致 E-钙黏蛋白增加,N-钙黏蛋白和波形蛋白表达减少。我们的研究表明,ADAM10 的高表达促进了 HSCC 的增殖和迁移。这些发现可能有助于为 HSCC 的治疗提供一种方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba75/5562066/3e267c63606a/OR-38-02-0866-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba75/5562066/b57661591a42/OR-38-02-0866-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba75/5562066/7dc19790be81/OR-38-02-0866-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba75/5562066/ee4a2918810b/OR-38-02-0866-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba75/5562066/d003e9b784bc/OR-38-02-0866-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba75/5562066/ab726edb8b8b/OR-38-02-0866-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba75/5562066/3e267c63606a/OR-38-02-0866-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba75/5562066/b57661591a42/OR-38-02-0866-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba75/5562066/7dc19790be81/OR-38-02-0866-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba75/5562066/ee4a2918810b/OR-38-02-0866-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba75/5562066/d003e9b784bc/OR-38-02-0866-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba75/5562066/ab726edb8b8b/OR-38-02-0866-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba75/5562066/3e267c63606a/OR-38-02-0866-g05.jpg

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Brain Res Bull. 2016 Sep;126(Pt 2):154-169. doi: 10.1016/j.brainresbull.2016.03.020. Epub 2016 Apr 7.
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