Periostin, secreted from stromal cells, has biphasic effect on cell migration and correlates with the epithelial to mesenchymal transition of human pancreatic cancer cells
Periostin, secreted from stromal cells, has biphasic effect on cell migration and correlates with the epithelial to mesenchymal transition of human pancreatic cancer cells
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DOI：
10.1002/ijc.23332
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发表时间：
2008-06-15
影响因子：
6.4
通讯作者：
Shimosegawa, Tooru
中科院分区：
文献类型：
--
作者：
Kanno, Atsushi;Satoh, Kennichi;Shimosegawa, Tooru
Periostin是一种分泌性蛋白，被认为是一种细胞黏附分子，可以促进肿瘤的侵袭性或生长速度。然而，它的表达与上皮向间充质转化(EMT)之间的关系尚不清楚，EMT被认为在癌细胞转移中起着关键作用。因此，作者调查了Periostin是否可能参与EMT的过程，以及该基因在胰腺癌发展中的作用。免疫组织化学和实时定量RT-PCR检测到Periostin主要在间质细胞中表达，而在癌细胞中很少表达。在体外，胰腺星状细胞(PSCs)表现出比癌细胞高得多的Periostin基础表达。表达Periostin的293T细胞培养上清液中分泌的Periostin(约150 ng/ml)可抑制胰腺癌细胞的迁移。共培养实验显示胰腺癌细胞可诱导PSC中Periostin的表达。为了评估Periostin在胰腺癌细胞中的直接作用，作者培育了稳定表达Periostin的胰腺癌细胞株。Periostin的诱导表达(至150 ng/ml)改变了癌细胞的形态，通过诱导上皮标记物和减少间充质标志物的表达，使癌细胞从间质表型转变为上皮表型，并在体外显示细胞迁移减少，形成较小的肿瘤，并抑制体内转移。高浓度的重组Periostin(1mU g/ml)通过激活AKT促进细胞迁移。研究结果提示，Periostin在胰腺癌的发生发展中具有双相作用。(C)2008年Wiley-Liss，Inc.
Periostin is a secretory protein that has been suggested to function as a cell adhesion molecule and promote the invasiveness or growth rate of tumors. However, little is known about the association of its expression and epithelial to mesenchymal transition (EMT), which is considered to play a crucial role in cancer cell metastasis. Thus, the authors investigated whether periostin could be involved in the process of EMT and the role of this gene in pancreatic cancer development. The expression of periostin was observed mainly in stromal cells but very little in cancer cells by immunohistochemistry and real-time RT-PCR. In vitro, pancreatic stellate cells (PSCs) exhibited a much higher basal expression of periostin compared with cancer cells. Periostin secreted in the supernatant from 293T cells that expressed periostin (approximately 150 ng/ml) inhibited the migration of pancreatic cancer cells. Coculture assay revealed that periostin expression in PSC was induced by pancreatic cancer cells. To assess the direct role of periostin in pancreatic cancer cells, the authors generated pancreatic cancer cell lines that stably express periostin. The induced expression of periostin (to 150 ng/ml) altered the morphology of cancer cells, changing them from mesenchymal to epithelial phenotypes with the induction of epithelial markers and a reduction of mesenchymal markers, and showed reduced cell migration in vitro and formed smaller tumors as well as suppressed metastasis in vivo. On the other hand, high concentration of recombinant periostin (1 mu g/ml) promoted cell migration with AKT activation. The findings suggest that periostin has biphasic effect on the development of pancreatic cancer. (C) 2008 Wiley-Liss, Inc.