N-cadherin expression is correlated with metastasis of spindle cell carcinoma of head and neck region
N-cadherin expression is correlated with metastasis of spindle cell carcinoma of head and neck region
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DOI：
10.1111/j.1600-0714.2010.00966.x
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发表时间：
2011-01-01
影响因子：
3.3
通讯作者：
Takata, Takashi
中科院分区：
文献类型：
--
作者：
Nguyen, Phuong T.;Kudo, Yasusei;Takata, Takashi
梭形细胞癌（SpCC）是一种由常规鳞状细胞癌和恶性梭形细胞成分组成的双相肿瘤。通过免疫组织化学分析，SpCC表达上皮和间充质标志物。越来越多的证据表明，上皮成分可以转化为肉瘤样细胞，这支持了SpCC是一种起源于干细胞的单克隆肿瘤，可以产生这两种成分的理论。E-cadherin的缺失和N-cadherin表达的增加被称为“cadherin切换”。钙粘蛋白转换是上皮-间质转化（EMT）的主要标志。EMT是癌症进展中的一个关键过程，为癌细胞提供了逃离主要病灶、侵入间质组织和迁移到远处区域的能力。虽然E-cadherin下调在多种癌症中是众所周知的，但关于N-cadherin在癌症中的表达的研究却很少。因此，我们研究了N-cadherin在头颈部SpCC进展中的表达。首先，我们在已建立的SpCC细胞系SpCC-1和SpCC-2中检测了钙粘蛋白的转换。SpCC-1和SpCC-2细胞呈纺锤形，呈钙粘蛋白切换。此外，我们通过免疫组织化学检测了15例SpCC患者N-cadherin的表达。虽然在非肿瘤性鳞状上皮中未观察到N-cadherin的表达，但在15例SpCC中有10例观察到N-cadherin的高表达。有趣的是，7例转移的SpCC中有6例显示N-cadherin高表达。综上所述，我们的研究结果表明N-cadherin除了在头颈部SpCC的发病机制中发挥重要作用外，还可能在SpCC的转移中发挥重要作用。
Spindle cell carcinoma (SpCC) is a biphasic tumor composed of conventional squamous cell carcinoma and a malignant spindle cell component. SpCC expresses both epithelial and mesenchymal markers by immunohistochemical analysis. There is mounting evidence for sarcomatoid transformation from the epithelial component, supporting the theory that SpCC is a monoclonal neoplasm originating from a stem cell giving rise to both components. The loss of E-cadherin and the gain of N-cadherin expression are known as the "cadherin switching". Cadherin switching is a major hallmark of epithelial-mesenchymal transition (EMT). EMT is a crucial process in cancer progression providing cancer cells with the ability to escape from the primary focus, to invade stromal tissues, and to migrate to distant regions. Although E-cadherin down-regulation is well known in various cancers, there are a few studies on N-cadherin expression in cancer. Here, therefore, we investigated N-cadherin expression in the progression of head and neck SpCC. First, we examined cadherin switching in our established SpCC cell lines, SpCC-1 and SpCC-2. SpCC-1 and SpCC-2 cells were spindle in shape and showed cadherin switching. Moreover, we examined N-cadherin expression in 15 SpCC cases by immunohistochemistry. Although N-cadherin expression was not observed in non-neoplastic squamous epithelium, high expression of N-cadherin was observed in 10 of 15 SpCC cases. Interestingly, 6 of 7 SpCC cases with metastasis showed high expression of N-cadherin. In conclusion, our findings suggest that N-cadherin may play an important role in metastasis of SpCC in addition to the pathogenesis of SpCC of the head and neck.