title: 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.
authors.affiliation: Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Muxing
authors.initials: M
authors.lastname: Kang
authors.forename: Biao
authors.initials: B
authors.lastname: Jiang
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Wenjie
authors.initials: W
authors.lastname: Lu
authors.forename: Qingqu
authors.initials: Q
authors.lastname: Guo
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Xie
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.forename: Daniel
authors.initials: D
authors.lastname: Chen
authors.forename: Yulian
authors.initials: Y
authors.lastname: Wu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002135:Calcium-Binding Proteins; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D051881:Receptor, Notch1 / Q000096:biosynthesis; D051883:Receptor, Notch2 / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000903:Antibiotics, Antineoplastic; D002135:Calcium-Binding Proteins; C424126:DLL4 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C497761:NOTCH1 protein, human; C497764:NOTCH2 protein, human; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D004317:Doxorubicin