SNAIL induces epithelial-to-mesenchymal transition in a human pancreatic cancer cell line (BxPC3) and promotes distant metastasis and invasiveness in vivo
SNAIL induces epithelial-to-mesenchymal transition in a human pancreatic cancer cell line (BxPC3) and promotes distant metastasis and invasiveness in vivo
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DOI：
10.1016/j.yexmp.2010.05.008
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发表时间：
2010-10-01
影响因子：
3.6
通讯作者：
Muragaki, Yasuteru
中科院分区：
文献类型：
--
作者：
Nishioka, Ryohei;Itoh, Shunji;Muragaki, Yasuteru
Snail是E-钙粘附素表达的有效抑制因子，在诱导上皮细胞向间充质转化(EMT)过程中起着关键作用。在EMT过程中，上皮细胞失去了细胞的极性和粘附性，并经历了剧烈的形态变化，获得了高度的迁移能力。尽管越来越多的证据表明EMT与某些人类癌症的进展有关，但它在胰腺癌进展中的意义仍然难以捉摸。在由转化生长因子-β1处理触发EMT的人胰腺癌细胞系PANC-1中，Snail和波形蛋白高表达，而E-钙粘附素表达很少。相比之下，另一种人类胰腺癌细胞株。未检测到蜗牛表达的BxPC3具有高水平的E-钙粘蛋白表达，并且不会在转化生长因子-β1治疗下进行EMT。然而，将蜗牛基因导入BxPC3细胞后，在没有添加任何生长因子的情况下，细胞进行了EMT，细胞形态和分子表达模式发生了显著变化。此外，在使用SCID小鼠的原位移植模型中，蜗牛转染的BxPC3显示出高度的转移和侵袭活性。在表达蜗牛的BxPC3来源的肿瘤的免疫组织化学分析中，在侵袭性肿瘤前沿观察到提示EMT的变化。Snail使BxPC3能够进行EMT，使其在体内具有高度恶性的潜能。这些结果表明，蜗牛介导的EMT可能与胰腺癌的进展有关，并且蜗牛可能是胰腺癌干预的分子靶点。(C)2010 Elsevier Inc.保留所有权利。
SNAIL, a potent repressor of E-cadherin expression, plays a key role in inducing epithelial-to-mesenchymal transition (EMT) in epithelial cells. During EMT, epithelial cells lose cell polarity and adhesion, and undergo drastic morphological changes acquiring highly migratory abilities. Although there is increasing evidence that EMT is involved in the progression of some human cancers, its significance in the progression of pancreatic cancer remains elusive. In Panc-1, a well-known human pancreatic cancer cell line in which EMT is triggered by TGF-beta 1 treatment, SNAIL and vimentin are highly expressed, whereas E-cadherin expression is scant. In contrast, another human pancreatic cancer cell line. BxPC3, in which SNAIL expression is not detected, has high levels of E-cadherin expression and does not undergo EMT upon TGF-beta 1 treatment. After transfecting the SNAIL gene into BxPC3, however, the cells undergo EMT with remarkable alterations in cell morphology and molecular expression patterns without the addition of any growth factors. Furthermore, in an orthotopic transplantation model using SCID mice, SNAIL-transfected BxPC3 displayed highly metastatic and invasive activities. In the immunohistochemical analysis of the tumor derived from the SNAIL-expressing BxPC3, alterations suggestive of EMT were observed in the invasive tumor front. SNAIL enabled BxPC3 to undergo EMT, endowing it with a highly malignant potential in vivo. These results indicate that SNAIL-mediated EMT may be relevant in the progression of pancreatic cancer, and SNAIL could be a molecular target for a pancreatic cancer intervention. (C) 2010 Elsevier Inc. All rights reserved.