Delta like ligand 4 induces impaired chemo-drug delivery and enhanced chemoresistance in pancreatic cancer

作者：Kang, Muxing; Jiang, Biao; Xu, Bin; Lu, Wenjie; Guo, Qingqu; Xie, Qiuping; Zhang, Bo; Dong, Xin; Chen, Daniel; Wu, Yulian^*

来源：Cancer Letters, 2013, 330(1): 11-21.

DOI：10.1016/j.canlet.2012.11.015

• DLL4
• Blood perfusion
• Chemoresistance
• Drug delivery
• Pancreatic cancer

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.

• 出版日期2013-3-1
• 单位浙江大学