title: Hypoxic Conditions Promote Gemcitabine Sensitivity in a Pancreatic Cancer Stem Cell Line.
abstract: Development of an effective therapeutic strategy for refractory pancreatic cancer must consider whether chemosensitivity can be induced in chemoresistant cells. We established a pancreatic cancer stem cell-rich cell line using TIG-1 feeder cells and leukemia inhibitory factor (LIF)-rich SNL76/7 conditioned medium. We generated a cell line, namely YNPC031312-B, following isolation of cells from the malignant ascites of a patient with gemcitabine-resistant pancreatic cancer. A YNPC031312-B-Hypoxia cell line was established by maintaining YNPC031312-B cells under tumor-like hypoxic conditions (1% O2). Both cell lines exhibited a pancreatic cancer stem cell phenotype: YNPC031312-B cells were CD24(+)CD44(-)CD133(+)epithelial cell adhesion molecule (EpCAM)(+)alkaline phosphatase(+)Octamer-binding transcription factor (OCT)3/4+and YNPC031312-B-Hypoxia cells were CD24(+)CD44(+)CD133(+)EpCAM(+). YNPC031312-B-Hypoxia cells were larger, had superior migratory ability, and higher gemcitabine sensitivity compared to YNPC031312-B cells. The use of LIF or other factors with similar bioactivity under hypoxic conditions may contribute to the phenotypic change to gemcitabine sensitivity. Our results may aid development of new therapeutic strategies targeting refractory pancreatic cancer.
authors: Shukoukai Inc., Tokyo, Japan.
authors: Akira
authors: A
authors: Imaizumi
authors: Departments of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan ohnishi@surg1.med.kyushu-u.ac.jp.
authors: Hideya
authors: H
authors: Onishi
authors: Departments of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Akio
authors: A
authors: Yamasaki
authors: Departments of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Makoto
authors: M
authors: Kawamoto
authors: Fukuoka General Cancer Clinic, Fukuoka, Japan.
authors: Masayo
authors: M
authors: Umebayashi
authors: Fukuoka General Cancer Clinic, Fukuoka, Japan.
authors: Takashi
authors: T
authors: Morisaki
authors: Shukoukai Inc., Tokyo, Japan.
authors: Kenichiro
authors: K
authors: Hasumi
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D000860:Hypoxia; D007124:Immunoenzyme Techniques; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D056892:Mediator Complex / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D053605:Leukemia Inhibitory Factor; C416944:MED15 protein, human; D056892:Mediator Complex; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Pancreatic cancer stem cell; gemcitabine resistance; hypoxia; leukemia inhibitory factor; phenotypic change