title: The differentiation of pancreatic tumor-initiating cells by vitronectin can be blocked by cilengitide.
abstract: OBJECTIVE
  Pancreatic cancer is a leading cancer type and its molecular pathology is poorly understood. The only potentially curative therapeutic option available is complete surgical resection; however, this is inadequate as most of the patients are diagnosed at an advanced or metastatic stage. Tumor-initiating cells (TICs) constitute a subpopulation of cells within a solid tumor that sustain tumor growth, metastasis, and chemo/radioresistance. Within pancreatic cancer, TICs have been identified based on the expression of specific cell surface markers.
  
  
  METHODS
  We use a sphere formation assay to enrich putative TICs and use human serum as a driver of differentiation. We demonstrate by using specific blocking reagents that we can inhibit the differentiation process and maintain TIC-associated markers and genes.
  
  
  RESULTS
  We can induce differentiation of pancreatospheres with the addition of human serum, and we identified vitronectin as an inducer of differentiation. We inhibit differentiation by human serum using an arginine-glycine-aspartate-specific peptide, which is Cilengitide; hence, demonstrating this differentiation is mediated via specific integrin receptors.
  
  
  CONCLUSIONS
  Overall, our studies further the definition of pancreatic TICs and provide further insight into both the maintenance and differentiation of this lethal population.
authors: Cancer Stem Cell Section, Laboratory of Cancer Prevention, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA. cabarcas002@gannon.edu
authors: Stephanie M
authors: SM
authors: Cabarcas
authors: Lei
authors: L
authors: Sun
authors: Lesley
authors: L
authors: Mathews
authors: Suneetha
authors: S
authors: Thomas
authors: Xiaohu
authors: X
authors: Zhang
authors: William L
authors: WL
authors: Farrar
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology; D019030:Receptors, Vitronectin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044967:Serum / Q000502:physiology; D012910:Snake Venoms / Q000494:pharmacology*; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D019096:Vitronectin / Q000494:pharmacology*
chemical_list: D014408:Biomarkers, Tumor; D039302:Integrin alphaVbeta3; D019030:Receptors, Vitronectin; D012910:Snake Venoms; D019096:Vitronectin; C064660:integrin alphaVbeta5; C422910:Cilengitide