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

Abstract
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.
AuthorsMuxing Kang, Biao Jiang, Bin Xu, Wenjie Lu, Qingqu Guo, Qiuping Xie, Bo Zhang, Xin Dong, Daniel Chen, Yulian Wu
JournalCancer letters (Cancer Lett) Vol. 330 Issue 1 Pg. 11-21 (Mar 01 2013) ISSN: 1872-7980 [Electronic] Ireland
PMID23200678 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Adaptor Proteins, Signal Transducing
  • Antibiotics, Antineoplastic
  • Calcium-Binding Proteins
  • DLL4 protein, human
  • Intercellular Signaling Peptides and Proteins
  • NOTCH1 protein, human
  • NOTCH2 protein, human
  • Receptor, Notch1
  • Receptor, Notch2
  • Doxorubicin
Topics
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antibiotics, Antineoplastic (pharmacology)
  • Calcium-Binding Proteins
  • Carcinoma, Pancreatic Ductal (drug therapy, metabolism, pathology)
  • Cell Line, Tumor
  • Doxorubicin (pharmacology)
  • Drug Delivery Systems
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins (biosynthesis, genetics, metabolism)
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Pancreatic Neoplasms (drug therapy, metabolism, pathology)
  • Receptor, Notch1 (biosynthesis)
  • Receptor, Notch2 (biosynthesis)
  • Xenograft Model Antitumor Assays

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