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

2012; Elsevier BV; Volume: 330; Issue: 1 Linguagem: Inglês

10.1016/j.canlet.2012.11.015

1872-7980

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

Epigenetics and DNA Methylation

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 chemo-drug delivery in vivo. Collectively, overexpressed DLL4 on neoplastic cells can enhance chemoresistance through angiogenesis-dependent/independent mechanisms in PDA.