Delta like ligand 4 induces impaired chemo-drug delivery and enhanced chemoresistance in pancreatic cancer
Delta like ligand 4 induces impaired chemo-drug delivery and enhanced chemoresistance in pancreatic cancer
复制标题
Delta 样配体 4 诱导胰腺癌化疗药物递送受损并增强化疗耐药性
DOI：
10.1016/j.canlet.2012.11.015
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发表时间：
2013-03-01
期刊：
影响因子：
9.7
通讯作者：
Wu, Yulian
中科院分区：
文献类型：
--
作者：
Kang, Muxing;Jiang, Biao;Wu, Yulian
胰腺导管腺癌（pancreatic ductal adenocarcinoma，PDA）的顽固性化疗耐药同时受到肿瘤实质和间质因素的影响，Notch配体Delta-like 4（DLL 4）在肿瘤恶性调节中的关键作用已被观察到。DLL 4在临床肿瘤导管细胞和癌旁组织中的阳性表达率差异有统计学意义，DLL 4/Notch通路的过度激活可增强EMT和肿瘤干细胞的表型，甚至可在体外诱导多药耐药。值得注意的是，伴随的缺陷性血管生成直接诱导体内低效的化疗药物递送。总的来说，肿瘤细胞上过表达的DLL 4可以通过PDA中的血管生成依赖性/非依赖性机制增强化疗耐药性。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
The stubborn chemoresistance of pancreatic ductal adenocarcinoma (PDA) is simultaneously influenced by tumor parenchymal and stromal factors, and the ctritical role of Notch ligand Delta-like 4 (DLL4) in the regulation of tumor malignancies has been observed. DLL4 positive expression ratio between duct cells from clinical tumor and adjacent tissues was statistically significant, and the overactivation of DLL4/Notch pathway enhanced the phenotype of EMT and cancer stem cell, even can induce multi-chemoresistance in vitro. Notably, the accompanied defective angiogenesis directly induced inefficient chemodrug delivery in vivo. Collectively, overexpressed DLL4 on neoplastic cells can enhance chemoresistance through angiogenesis-dependent/independent mechanisms in PDA. (C) 2012 Elsevier Ireland Ltd. All rights reserved.