PGRN promotes migration and invasion of epithelial ovarian cancer cells through an epithelial mesenchymal transition program and the activation of cancer associated fibroblasts
PGRN promotes migration and invasion of epithelial ovarian cancer cells through an epithelial mesenchymal transition program and the activation of cancer associated fibroblasts
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DOI：
10.1016/j.yexmp.2015.11.021
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发表时间：
2016-02-01
影响因子：
3.6
通讯作者：
Wang, Linlin
中科院分区：
文献类型：
--
作者：
Dong, Taotao;Yang, Dong;Wang, Linlin
在本文中，我们旨在探讨颗粒体蛋白前体（PGRN）是否可以直接诱导上皮性卵巢癌细胞经历上皮间质转化（EMT）程序，并通过其间接激活癌症相关成纤维细胞（CAF）。对78例上皮性卵巢癌（EOC）患者组织样本进行免疫组化（IHC）染色发现，PGRN表达水平与E-cadherin水平呈负相关（r=-0.289，P=0.013），与Slug水平呈正相关（r=0.332，P=0.003）；细胞实验表明，PGRN过表达可以显着增加A2780细胞的迁移和侵袭能力。此外，高剂量（62 ng/ml）的重组PGRN可以诱导人正常成纤维细胞中平滑肌肌动蛋白α（α-SMA）的高表达14.7倍。此外，组织样本中 PGRN 和 α-SMA 水平较高的患者比 PGRN 或 α-SMA 水平较低的患者无病生存期 (DFS) 和总生存期 (OS) 最差。所有结果表明PGRN可以通过直接EMT程序和间接激活CAF来促进EOC细胞的侵袭性。这可能为EOC提供新的有效治疗靶点。 (C) 2015 Elsevier Inc. 保留所有权利。
In this paper, we aimed to explore whether progranulin (PGRN) could induce epithelial ovarian cancer cells to undergo an epithelial mesenchymal transition (EMT) program directly and through its activation of cancer associated fibroblasts (CAFs) indirectly. Immunohistochemistry(IHC) staining of tissue samples of 78 cases of epithelial ovarian cancer (EOC) patients found that PGRN expression levels were negatively correlated with E-cadherin levels (r = -0.289, P = 0.013) and positively correlated with Slug levels (r = 0.332, P = 0.003); Cell experiments showed that PGRN overexpression could increase the migratory and invasive abilities of A2780 cells significantly. Moreover, high doses (62 ng/ml) of recombinant PGRN could induce 14.7 fold high expression of smooth muscle actin alpha (alpha-SMA) in human normal fibroblasts. In addition, patients with both high levels of PGRN and alpha-SMA in their tissue samples had the worst disease free survival (DFS) and overall survival (OS) than those with low levels of PGRN or alpha-SMA. All the results suggest that PGRN could promote invasiveness of EOC cells through an EMT program directly and through activation of CAFs indirectly. This may provide a new effective therapy target for EOC. (C) 2015 Elsevier Inc. All rights reserved.