TWIST1 upregulation affects E-cadherin expression in brain metastases
TWIST1 upregulation affects E-cadherin expression in brain metastases
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DOI：
10.1007/s12094-020-02496-3
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发表时间：
2020-10-01
影响因子：
3.4
通讯作者：
Pecina-Slaus, N.
中科院分区：
文献类型：
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作者：
Brlek, P.;Bukovac, A.;Pecina-Slaus, N.
目的E-钙粘蛋白是一种钙依赖性糖蛋白，其主要作用是细胞间粘附。其转录抑制因子TWIST 1是一种碱性螺旋-环-螺旋（bHLH）蛋白，参与胚胎发生过程中原肠胚形成和中胚层组织的形成。在成人组织中，TWIST 1的高表达诱导上皮-间质转化（EMT）-细胞变得能动并能够转移的过程。在本文中，我们研究了E-cadherin和TWIST 1在两个不同的原发部位-乳腺和肺的脑转移瘤的癌变过程中的作用。方法应用免疫组织化学方法和特异性单克隆抗体检测E-cadherin及其转录抑制因子TWIST 1在人乳腺癌组织中的定位和表达。采用Image J软件进行半定量分析，H评分进行统计学评价。结果免疫组化显示85.7%的脑转移瘤中E-cadherin表达下调，82.2%的脑转移瘤中TWIST 1表达上调。统计学分析证实TWIST 1和E-cadherin的表达之间存在显著的负相关性（p= 0.001）。当将脑转移瘤表达水平与相应患者中的原发性乳腺肿瘤进行比较时，与相应转移瘤相比，E-钙粘蛋白在原发对中显示出更高的表达。与其作用一致，与相应的转移对相比，TWIST 1在所有原发性肿瘤样品中下调（p= 0.034）。结论本研究为脑转移瘤的诊断和治疗提供了有价值的分子生物学数据，为脑转移瘤的诊断和治疗提供了新的可能性。
Purpose E-cadherin is a calcium-dependent glycoprotein whose main role is cell-cell adhesion. Its transcriptional repressor TWIST1 is a basic helix-loop-helix (bHLH) protein that participates in gastrulation and formation of mesodermal tissues during embryogenesis. In adult tissues, the high expression of TWIST1 induces the epithelial-mesenchymal transition (EMT)-a process in which cells become motile and able to metastasize. In this paper, we investigated the involvement of E-cadherin and TWIST1 in the carcinogenesis of brain metastases originating from two different primary sites-breast and lung. Methods The localization and expression of E-cadherin and its transcriptional repressor TWIST1 were investigated using a DAB-labeled streptavidin-horseradish peroxidase immunohistochemical reaction and specific monoclonal antibodies against TWIST1 and E-cadherin. Image J software was used for semi-quantitative analysis while H-score served for statistical evaluations. Results Immunohistochemistry showed that the expression of E-cadherin was downregulated in 85.7% of brain metastases, while at the same time, 82.2% of them showed upregulated TWIST1. Statistical analysis confirmed a significant negative correlation between expressions of TWIST1 and E-cadherin (p= 0.001). When the brain metastases expression levels were compared to primary breast tumors in corresponding patients, E-cadherin showed higher expression in primary pairs compared to corresponding metastases. Consistent to its role, TWIST1 was downregulated in all primary tumor samples in comparison to corresponding metastases pairs (p= 0.034). Conclusion This research provides valuable data regarding molecular events involving two EMT key components that could give directions for new possibilities for brain metastases diagnosis and treatment.