Restoration of E-cadherin expression by selective Cox-2 inhibition and the clinical relevance of the epithelial-to-mesenchymal transition in head and neck squamous cell carcinoma.
Restoration of E-cadherin expression by selective Cox-2 inhibition and the clinical relevance of the epithelial-to-mesenchymal transition in head and neck squamous cell carcinoma.
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DOI：
10.1186/1756-9966-33-40
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发表时间：
2014-05-10
期刊：
影响因子：
--
通讯作者：
Ogawa K
中科院分区：
文献类型：
--
作者：
Fujii R;Imanishi Y;Shibata K;Sakai N;Sakamoto K;Shigetomi S;Habu N;Otsuka K;Sato Y;Watanabe Y;Ozawa H;Tomita T;Kameyama K;Fujii M;Ogawa K
上皮-间质转化（EMT）伴随着E-钙粘蛋白的下调被认为是促进转移。环氧合酶-2（考克斯-2）被认为通过其多方面的功能促进癌症进展，最近提出了其与E-钙粘蛋白的反比关系。本研究的目的是探讨选择性考克斯-2抑制剂是否能恢复头颈部鳞状细胞癌（HNSCC）细胞中E-cadherin的表达，并检测EMT相关分子的表达水平与HNSCC临床病理因素的可能相关性。我们使用定量实时PCR来检测三种选择性考克斯-2抑制剂的作用，即，塞来昔布、NS-398和SC-791对人HNSCC细胞系HSC-2和HSC-4中E-钙粘蛋白（CDH-1）及其转录抑制因子（SIP1、Snail、Twist）基因表达的影响。为了评估细胞表面E-钙粘蛋白表达的变化，我们使用了流式细胞仪和免疫荧光染色，除了蛋白质印迹。对40例舌鳞状细胞癌（TSCC）的临床病理因素和考克斯-2、CDH-1及其抑制因子mRNA的表达进行分析。选择性考克斯-2抑制剂通过下调HNSCC细胞表面E-cadherin的转录抑制因子而上调其表达。这种影响的程度取决于每个细胞系中E-钙粘蛋白和考克斯-2的基线表达水平。单因素分析显示，考克斯-2 mRNA高表达（p = 0.037）、CDH-1 mRNA低表达（p = 0.020）和T分期高（p = 0.036）与TSCC淋巴结转移显著相关。多因素Logistic回归分析显示CDH-1 mRNA表达降低是影响淋巴结转移的独立危险因素（p = 0.041）。这些发现表明，适当选择性给予某些考克斯-2抑制剂可能通过恢复E-钙粘蛋白表达抑制EMT而具有抗转移作用。此外，CDH-1表达下调可能与TSCC的淋巴结转移密切相关。
The epithelial-to-mesenchymal transition (EMT) accompanied by the downregulation of E-cadherin has been thought to promote metastasis. Cyclooxygenase-2 (Cox-2) is presumed to contribute to cancer progression through its multifaceted function, and recently its inverse relationship with E-cadherin was suggested. The aim of the present study was to investigate whether selective Cox-2 inhibitors restore the expression of E-cadherin in head and neck squamous cell carcinoma (HNSCC) cells, and to examine the possible correlations of the expression levels of EMT-related molecules with clinicopathological factors in HNSCC. We used quantitative real-time PCR to examine the effects of three selective Cox-2 inhibitors, i.e., celecoxib, NS-398, and SC-791 on the gene expressions of E-cadherin (CDH-1) and its transcriptional repressors (SIP1, Snail, Twist) in the human HNSCC cell lines HSC-2 and HSC-4. To evaluate the changes in E-cadherin expression on the cell surface, we used a flowcytometer and immunofluorescent staining in addition to Western blotting. We evaluated and statistically analyzed the clinicopathological factors and mRNA expressions of Cox-2, CDH-1 and its repressors in surgical specimens of 40 patients with tongue squamous cell carcinoma (TSCC). The selective Cox-2 inhibitors upregulated the E-cadherin expression on the cell surface of the HNSCC cells through the downregulation of its transcriptional repressors. The extent of this effect depended on the baseline expression levels of both E-cadherin and Cox-2 in each cell line. A univariate analysis showed that higher Cox-2 mRNA expression (p = 0.037), lower CDH-1 mRNA expression (p = 0.020), and advanced T-classification (p = 0.036) were significantly correlated with lymph node metastasis in TSCC. A multivariate logistic regression revealed that lower CDH-1 mRNA expression was the independent risk factor affecting lymph node metastasis (p = 0.041). These findings suggest that the appropriately selective administration of certain Cox-2 inhibitors may have an anti-metastatic effect through suppression of the EMT by restoring E-cadherin expression. In addition, the downregulation of CDH-1 resulting from the EMT may be closely involved in lymph node metastasis in TSCC.
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影响因子：
8.8
作者：
Adhim, Z.;Matsuoka, T.;Bito, T.;Shigemura, K.;Lee, K-M;Kawabata, M.;Fujisawa, M.;Nibu, K.;Shirakawa, T.
通讯作者：
Shirakawa, T.
影响因子：
3.3
作者：
Bánkfalvi, A;Krassort, M;Piffkó, J
通讯作者：
Piffkó, J
下调E-钙粘蛋白（ECAD） - 在口腔和口咽早期鳞状细胞癌的前哨淋巴结活检中，神秘转移性疾病的预测因子。
影响因子：
3.8
作者：
Huber GF;Züllig L;Soltermann A;Roessle M;Graf N;Haerle SK;Studer G;Jochum W;Moch H;Stoeckli SJ
通讯作者：
Stoeckli SJ
影响因子：
4.8
作者：
Gallo, O;Franchi, A;Masini, E
通讯作者：
Masini, E
DOI：
10.1093/jnci/djk112
发表时间：
2007-04-04
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Heath, Elisabeth I.;Canto, Marcia Irene;Forastiere, Arlene A.
通讯作者：
Forastiere, Arlene A.