title: Chemoresistance is associated with cancer stem cell-like properties and epithelial-to-mesenchymal transition in pancreatic cancer cells.
abstract: BACKGROUND
  The aim of this study was to evaluate whether apoptosis-resistant cancer cells have cancer stem cell (CSC)-like properties.
  
  
  METHODS
  Panc-1 pancreatic cancer cells were incubated in the presence of 5-fluorouracil (5-FU) for 24 h, and further incubated without 5-FU for 28 days. To assess the capacity of self-renewal, surviving cells were planted for sphere-forming assay. Epithelial-to-mesenchymal transition (EMT) was induced with TGF-β, then mRNA expression was evaluated by real-time PCR for E-cadherin, SNAIL, and vimentin. The E-Cadherin protein levels were also examined by immunoblot analysis. The Local invasion ability was analyzed by Matrigel invasion assay.
  
  
  RESULTS
  The frequency of cells that were capable of initiating spheres was higher in 5-FU-pre treated cells, which also overexpressed stem cell marker genes, OCT4 and NANOG. Matrigel invasion activity of apoptosis-resistant Panc-1 cells was greater than that of control Panc-1 cells.
  
  
  CONCLUSIONS
  Apoptosis-resistant cancer cells have CSC-like properties, i.e., able to initiate sphere formation, express stem cell genes, and respond to EMT stimulation.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine,Keio University School of Medicine, Tokyo, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Izumiya
authors.forename: Ayano
authors.initials: A
authors.lastname: Kabashima
authors.forename: Hajime
authors.initials: H
authors.lastname: Higuchi
authors.forename: Toru
authors.initials: T
authors.lastname: Igarashi
authors.forename: Gen
authors.initials: G
authors.lastname: Sakai
authors.forename: Hideko
authors.initials: H
authors.lastname: Iizuka
authors.forename: Shoko
authors.initials: S
authors.lastname: Nakamura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Adachi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hamamoto
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Funakoshi
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Takaishi
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D005472:Fluorouracil / Q000494:pharmacology*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000473:pathology*; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D000964:Antimetabolites, Antineoplastic; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D016212:Transforming Growth Factor beta; D005472:Fluorouracil