title: Characteristics of Notch2(+) pancreatic cancer stem-like cells and the relationship with centroacinar cells.
abstract: Notch2, a surface marker in cell lines, is used to isolate, identify and localise pancreatic cancer stem-like cells and is a target for therapy of these cells. Sphere formation was induced in Panc-1 and Bxpc-3 pancreatic cancer cell lines, and Notch2(+) cells were separated from Bxpc-3 and Panc-1 cell lines by magnetic activated cell sorting (MACS). Expression of stem cell-related markers, OCT4, Nanog and PDX1, were measured by immunofluorescent (IF) staining. Expression of Notch2 was also determined immunohistochemically in pancreatic tissues. Notch2(+) cells were transplanted in subcutaneous of mice. AQP1 and AQP5 were also measured by IF in Bxpc-3 cells. The Notch signal pathway inhibitor, Compound E (CE), was used to treat Notch2(+) Bxpc-3 cells, and their vitalities were subsequently measured by the CCK-8 method. Positive expression of OCT4, Nanog and PDX1 was observed in Notch2(+) cells. Notch2(+) cells at centroacinar cell (CAC) and terminal ductal locations expressed AQP1 and AQP5. They were strongly tumourigenic in mice, and CE inhibited proliferation of Notch2(+) Bxpc-3 cells to some degree. OCT4 and Nanog can be used as markers of self-renewal in pancreatic cancer stem cells. Notch2(+) cells in human pancreatic cancer Bxpc-3 and Panc-1 cell lines had the properties of cancer stem cells. The results suggest that Notch2(+) pancreatic cancer stem-like cells had a close relationship with CAC.
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Zhu-Chao
authors.initials: ZC
authors.lastname: Zhou
authors.forename: Qiang-Gang
authors.initials: QG
authors.lastname: Dong
authors.forename: De-Liang
authors.initials: DL
authors.lastname: Fu
authors.forename: Yi-Yi
authors.initials: YY
authors.lastname: Gong
authors.forename: Quan-Xing
authors.initials: QX
authors.lastname: Ni
mesh_terms: D061354:Acinar Cells / Q000378:metabolism*; D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism; D051402:Aquaporin 5 / Q000235:genetics / Q000378:metabolism; D063646:Carcinogenesis / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival; D002478:Cells, Cultured; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D000071317:Nanog Homeobox Protein; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051883:Receptor, Notch2 / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism
chemical_list: C496020:AQP1 protein, human; C496036:AQP5 protein, human; D051402:Aquaporin 5; D018398:Homeodomain Proteins; C486780:NANOG protein, human; C497764:NOTCH2 protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D051883:Receptor, Notch2; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D051398:Aquaporin 1
keywords: Notch; cancer stem cells; centroacinar cells; pancreatic cancer