title: Retinoic Acid Reduces Stem Cell-Like Features in Pancreatic Cancer Cells.
abstract: OBJECTIVE
  Retinoic acid (RA) has important functions during embryonic development being involved in cell growth and differentiation. Although approved for the treatment of acute promyelocytic leukemia, it is still under investigation for different solid tumors including pancreatic cancer. The objective of this study was to analyze how RA affects pancreatic cancer stem cells and how its combination with chemotherapy could impact cell growth.
  
  
  METHODS
  Using different pancreatic cancer cell lines, we evaluated the effect of RA alone or in combination with chemotherapy regulating cancer stem cells properties and pathways.
  
  
  RESULTS
  Retinoic acid treatment reduces the expression of pancreatic stem cell markers CD24, CD44, CD133, and aldehyde dehydrogenase 1 but not c-Met. Although gemcitabine treatment increases the expression of some of these markers especially CD44 when it is combined with RA, a notable reduction in all of them is observed. Retinoic acid induces a G0/G1 arrest and combined with gemcitabine increases the apoptotic effect produced by chemotherapy probably as a consequence of a regulation of specific stem cell transcription factors.
  
  
  CONCLUSIONS
  Retinoic acid regulates self-renewal capacity of cells in pancreatic tumors and should be further investigated in combination with chemotherapy as therapeutic strategy in pancreatic cancer.
authors.affiliation: From the *Division of Oncology Research, Schulze Center for Novel Therapeutics, College of Medicine, Mayo Clinic, Rochester, MN; †Department of Gastroenterology, Hospital Donostia/Biodonostia Institute, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad del País Vasco UPV/EHU, San Sebastian, Spain; ‡Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University; and §Division of Molecular Diagnostics, Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Marta
authors.initials: M
authors.lastname: Herreros-Villanueva
authors.forename: Tze-Kiong
authors.initials: TK
authors.lastname: Er
authors.forename: Luis
authors.initials: L
authors.lastname: Bujanda
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D014157:Transcription Factors; D003841:Deoxycytidine; D014212:Tretinoin; D005472:Fluorouracil; D000093542:Gemcitabine