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自口腔癌发生的早期阶段起,E-钙黏蛋白和SNAIL的亚细胞定位及表达就具有相关性。

Subcellular localization and expression of E-cadherin and SNAIL are relevant since early stages of oral carcinogenesis.

作者信息

Lopes Nathália Martins, Xavier Flávia Caló Aquino, Ortiz Rafael Carneiro, Amôr Nádia Ghinelli, Garlet Gustavo Pompermaier, Lara Vanessa Soares, Batista Aline Carvalho, Costa Nádia Lago, Rodini Camila Oliveira

机构信息

Department of Biological Sciences, Bauru School of Dentistry - University of Sao Paulo, Alameda Dr. Octávio Pinheiro Brisolla, 9-75, Bauru, SP, 17.012-901, Brazil.

Laboratory of Oral Surgical Pathology, School of Dentistry - Federal University of Bahia, Araújo Pinho Avenue, 62, 9th floor, Salvador, BA, 40.110-150, Brazil.

出版信息

Pathol Res Pract. 2018 Aug;214(8):1185-1191. doi: 10.1016/j.prp.2018.06.004. Epub 2018 Jun 20.

Abstract

The biological process of epithelial-to-mesenchymal transition (EMT) has been studied in oral squamous cell carcinoma (OSCC) metastasis, but it is rarely evaluated at several stages of oral carcinogenesis. This study aimed to analyze the presence of SNAIL and E-cadherin proteins, markers of EMT, in the development and progression of OSCC, evaluating excised specimens of potentially malignant lesions (oral leukoplakia with and without dysplasia-OL and OLD, respectively), tumor tissues (OSCC), metastatic lymph nodes (LN), and normal oral mucosa (NOM) by immunohistochemistry, considering subcellular localization. Additionally, SNAIL and E-cadherin transcripts were evaluated in vitro by qPCR, using SCC-9 cell line in comparison to human keratinocytes (HPEC). There was a significant increase in nuclear expression of SNAIL from NOM to OLD followed by a noticeable decrease in nuclear expression accompanied by increased cytoplasmic expression in OSCC (p<0.05). The E-cadherin cytoplasmic expression was remarkable and statistically significant higher in OSCC and LN, both compared to NOM (p< 0.0001), OL (p<0.01) and OLD (p< 0.0001 and p<0.001, respectively). In vitro, E-cadherin and SNAIL transcripts were lower in SCC-9 compared to HPEC cells, although only the decrease of E-cadherin was statistically significant (p<0.05). Regarding the association of E-cadherin and SNAIL expression with the clinical findings, the analysis revealed an association between the cytoplasmic expression of SNAIL and the invasion pattern (p=0.05) in OSCC. The increased nuclear SNAIL expression may be characteristic of OLD, and the presence of E-cadherin in cell cytoplasm a marker of transformation to malignancy of potentially malignant oral leukoplakias into OSCC.

摘要

上皮-间质转化(EMT)的生物学过程已在口腔鳞状细胞癌(OSCC)转移中得到研究,但在口腔癌发生的几个阶段很少进行评估。本研究旨在分析EMT标志物SNAIL和E-钙黏蛋白在OSCC发生发展过程中的表达情况,通过免疫组织化学方法评估潜在恶性病变(分别为伴有和不伴有发育异常的口腔白斑 - OL和OLD)、肿瘤组织(OSCC)、转移淋巴结(LN)和正常口腔黏膜(NOM)的切除标本,并考虑亚细胞定位。此外,使用SCC - 9细胞系与人角质形成细胞(HPEC)进行比较,通过qPCR在体外评估SNAIL和E-钙黏蛋白转录本。从NOM到OLD,SNAIL的核表达显著增加,随后在OSCC中核表达明显下降,同时细胞质表达增加(p<0.05)。与NOM(p<0.0001)、OL(p<0.01)和OLD(分别为p<0.0001和p<0.001)相比,E-钙黏蛋白的细胞质表达在OSCC和LN中显著且具有统计学意义的升高。在体外,与HPEC细胞相比,SCC - 9细胞中E-钙黏蛋白和SNAIL转录本较低,尽管只有E-钙黏蛋白的下降具有统计学意义(p<0.05)。关于E-钙黏蛋白和SNAIL表达与临床结果的相关性分析显示,OSCC中SNAIL的细胞质表达与侵袭模式之间存在关联(p = 0.05)。SNAIL核表达增加可能是OLD的特征,而E-钙黏蛋白在细胞质中的存在是潜在恶性口腔白斑向OSCC恶性转化的标志物。

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