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上皮生长因子对肿瘤发生模型中基质金属蛋白酶-2及E-钙黏蛋白/β-连环蛋白表达的影响

Effect of epithelial growth factor on matrix metalloproteinase-2 and E-cadherin/β-catenin expression in an model of tumorigenesis.

作者信息

Navarini Natalia Festugatto, De Araújo Vera Cavalcanti, Sperandio Marcelo, Napimoga Marcelo Henrique, Teixeira Lucas Novaes, De Araújo Ney Soares, Martinez Elizabeth Ferreira

机构信息

Department of Oral Pathology, São Leopoldo Mandic Institute and Research Center, Campinas, São Paulo 13045-755, Brazil.

Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Research Center, Campinas, São Paulo 13045-755, Brazil.

出版信息

Oncol Lett. 2017 Sep;14(3):3136-3140. doi: 10.3892/ol.2017.6513. Epub 2017 Jun 30.

Abstract

The aim of the present study was to analyze the effect of various doses of epidermal growth factor (EGF; 5 and 10 ng/ml) on matrix metalloproteinase-2 (MMP-2) secretion and E-cadherin/β-catenin expression by co-cultured cells that mimic an carcinoma ex-pleomorphic adenoma, where benign myoepithelial cells from a pleomorphic adenoma surround malignant epithelial cells. EGF was supplemented in various doses and the effects were evaluated following four days of cell culture. ELISA was performed to determine MMP-2 secretion levels. Gene expression for E-cadherin and β-catenin was analyzed using quantitative polymerase chain reaction. The results revealed that E-cadherin expression decreased when the cells were supplemented with 5 ng/ml EGF. ELISA results indicated that MMP-2 secretion increased when EGF was supplemented at concentrations of 5 and 10 ng/ml. The present findings demonstrated that EGF may be involved in the epithelial-mesenchymal transition process via altering the E-cadherin/β-catenin complex and increasing MMP-2 secretion, which may then favor the dissolution of the basement membrane to the benefit of malignant cell clusters, contributing to the development of an invasive phenotype in this model of tumorigenesis.

摘要

本研究的目的是分析不同剂量的表皮生长因子(EGF;5和10 ng/ml)对模拟癌性多形性腺瘤的共培养细胞中基质金属蛋白酶-2(MMP-2)分泌以及E-钙黏蛋白/E-连环蛋白表达的影响,在该模型中,多形性腺瘤的良性肌上皮细胞围绕着恶性上皮细胞。以不同剂量补充EGF,并在细胞培养4天后评估其效果。采用酶联免疫吸附测定(ELISA)来确定MMP-2的分泌水平。使用定量聚合酶链反应分析E-钙黏蛋白和E-连环蛋白的基因表达。结果显示,当细胞补充5 ng/ml EGF时,E-钙黏蛋白表达下降。ELISA结果表明,当以5和10 ng/ml的浓度补充EGF时,MMP-2分泌增加。本研究结果表明,EGF可能通过改变E-钙黏蛋白/E-连环蛋白复合物并增加MMP-2分泌而参与上皮-间质转化过程,这可能有利于基底膜的溶解,从而有利于恶性细胞簇的生长,促进该肿瘤发生模型中侵袭性表型的发展。

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