title: Pancreatic cancer cells resistant to chemoradiotherapy rich in "stem-cell-like" tumor cells.
abstract: BACKGROUND
  Tumor resistance to chemoradiation therapy is partly attributed to the presence of apoptosis-resistant cancer stem cells (CSCs). Chemoradiation therapy can enrich CSCs by killing apoptosis-susceptible cancer cells.
  
  
  OBJECTIVE
  Our preliminary study showed chemoradiation-resistant pancreatic cancer cells to have some CSC characteristics, and to undergo epithelial-mesenchymal transition (EMT); we aimed to verify that study's implication that chemoradiation-resistant subpopulations are enriched with "stem-cell-like" tumor cells, which may be linked to EMT.
  
  
  METHODS
  Four pancreatic cancer cell lines were cultured in gemcitabine with synchronous radiotherapy to obtain resistant subpopulations. Morphological changes were observed under microscope; migration and invasiveness were assessed by Transwell tests. Protein expression was determined by immunoblotting. Pancreatic CSC markers were studied using fluorescence-activated cell sorting analyses. Colony-formation tests, tumor sphere formation assays, and tumor xenografts in BALB/C nude mice were used to evaluate "stemness" in resistant cells.
  
  
  RESULTS
  Resistant cells expressed more antiapoptotic protein Bcl-2, apoptosis-inhibitory protein survivin, and stem cell markers Oct4, ABCG2, CD24, and CD133, were more tumorigenic in vitro and in vivo, and showed phenotypic and molecular changes consistent with EMT, including upregulation of vimentin and downregulation of E-cadherin. They were also more invasive and migratory.
  
  
  CONCLUSIONS
  We found chemoradiation-resistant pancreatic cancer cells to be similar to CSCs and to undergo EMT, suggesting that chemoradiation resistance-induced EMT is linked to CSC generation.
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University Medical School, 200025, Shanghai, People's Republic of China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Du
authors.forename: Renyi
authors.initials: R
authors.lastname: Qin
authors.forename: Cuifeng
authors.initials: C
authors.lastname: Wei
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Chengjian
authors.initials: C
authors.lastname: Shi
authors.forename: Rui
authors.initials: R
authors.lastname: Tian
authors.forename: Chenghong
authors.initials: C
authors.lastname: Peng
mesh_terms: D000071916:AC133 Antigen; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D051927:CD24 Antigen / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D006023:Glycoproteins; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011836:Radiation Tolerance; D000077022:Survivin; D014746:Vimentin / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: C116614:ABCG2 protein, human; D000071916:AC133 Antigen; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; C107489:BIRC5 protein, human; D051927:CD24 Antigen; C497889:CD24 protein, human; D015820:Cadherins; D006023:Glycoproteins; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D014746:Vimentin; D003841:Deoxycytidine; D000093542:Gemcitabine