Irradiated fibroblasts promote epithelial-mesenchymal transition and HDGF expression of esophageal squamous cell carcinoma
Irradiated fibroblasts promote epithelial-mesenchymal transition and HDGF expression of esophageal squamous cell carcinoma
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DOI：
10.1016/j.bbrc.2015.02.001
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发表时间：
2015-03-06
影响因子：
3.1
通讯作者：
Cheng, Yu-Feng
中科院分区：
文献类型：
--
作者：
Bao, Ci-Hang;Wang, Xin-Tong;Cheng, Yu-Feng
最近的证据表明，未辐照的癌症相关成纤维细胞（CAFs）通过上皮间充质转化（EMT）促进癌细胞的侵袭性表型。肝癌源性生长因子（HDGF）是食管鳞状细胞癌（ESCC）的一个放射敏感基因。本研究旨在探讨辐照成纤维细胞对ESCC细胞EMT和HDGF表达的影响。我们的研究表明，与未辐照成纤维细胞共培养可显著提高ESCC细胞的侵袭能力，且与辐照成纤维细胞共培养可进一步加速ESCC细胞侵袭能力的增强。受辐照成纤维细胞的上清液也加速了ESCC细胞的散射。将ESCC细胞暴露于辐照成纤维细胞的上清液中，体外实验结果表明，Ecadherin减少，vimentin增加，体内实验结果表明-catenin在辐照成纤维细胞的肿瘤细胞中定位于细胞核。体外和体内模型辐照组成纤维细胞和ESCC细胞中HDGF和P-catenin的表达均升高。有趣的是，与间质成纤维细胞相邻的肿瘤细胞表现出强烈的核HDGF免疫反应性，这表明成纤维细胞对HDGF表达有旁分泌作用。这些数据表明，辐照成纤维细胞促进ESCC的侵袭、生长、EMT和HDGF表达。(C) 2015爱思唯尔公司版权所有。
Recent evidence suggested that nonirradiated cancer-associated fibroblasts (CAFs) promoted aggressive phenotypes of cancer cells through epithelial mesenchymal transition (EMT). Hepatoma-derived growth factor (HDGF) is a radiosensitive gene of esophageal squamous cell carcinoma (ESCC). This study aimed to investigate the effect of irradiated fibroblasts on EMT and HDGF expression of ESCC. Our study demonstrated that coculture with nonirradiated fibroblasts significantly increased the invasive ability of ESCC cells and the increased invasiveness was further accelerated when they were cocultured with irradiated fibroblasts. Scattering of ESCC cells was also accelerated by the supernatant from irradiated fibroblasts. Exposure of ESCC cells to supernatant from irradiated fibroblasts resulted in decreased Ecadherin, increased vimentin in vitro and beta-catenin was demonstrated to localize to the nucleus in tumor cells with irradiated fibroblasts in vivo models. The expression of HDGF and P-catenin were increased in both fibroblasts and ESCC cells of irradiated group in vitro and in vivo models. Interestingly, the tumor cells adjoining the stromal fibroblasts displayed strong nuclear HDGF immunoreactivity, which suggested the occurrence of a paracrine effect of fibroblasts on HDGF expression. These data suggested that irradiated fibroblasts promoted invasion, growth, EMT and HDGF expression of ESCC. (C) 2015 Elsevier Inc. All rights reserved.