title: Co-Expression of Cancer Stem Cell Markers Corresponds to a Pro-Tumorigenic Expression Profile in Pancreatic Adenocarcinoma.
abstract: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. Its dismal prognosis is often attributed to the presence of cancer stem cells (CSCs) that have been identified in PDAC using various markers. However, the co-expression of all of these markers has not yet been evaluated. Furthermore, studies that compare the expression levels of CSC markers in PDAC tumor samples and in cell lines derived directly from those tumors are lacking. Here, we analyzed the expression of putative CSC markers-CD24, CD44, epithelial cell adhesion molecule (EpCAM), CD133, and nestin-by immunofluorescence, flow cytometry and quantitative PCR in 3 PDAC-derived cell lines and by immunohistochemistry in 3 corresponding tumor samples. We showed high expression of the examined CSC markers among all of the cell lines and tumor samples, with the exception of CD24 and CD44, which were enriched under in vitro conditions compared with tumor tissues. The proportions of cells positive for the remaining markers were comparable to those detected in the corresponding tumors. Co-expression analysis using flow cytometry revealed that CD24+/CD44+/EpCAM+/CD133+ cells represented a significant population of the cells (range, 43 to 72%) among the cell lines. The highest proportion of CD24+/CD44+/EpCAM+/CD133+ cells was detected in the cell line derived from the tumor of a patient with the shortest survival. Using gene expression profiling, we further identified the specific pro-tumorigenic expression profile of this cell line compared with the profiles of the other two cell lines. Together, CD24+/CD44+/EpCAM+/CD133+ cells are present in PDAC cell lines derived from primary tumors, and their increased proportion corresponds with a pro-tumorigenic gene expression profile.
authors.affiliation: Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.|Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.|International Clinical Research Center, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Skoda
authors.affiliation: 1st Department of Pathological Anatomy, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Marketa
authors.initials: M
authors.lastname: Hermanova
authors.affiliation: Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Loja
authors.affiliation: Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Nemec
authors.affiliation: Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.|Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.|International Clinical Research Center, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Jakub
authors.initials: J
authors.lastname: Neradil
authors.affiliation: Department of Complex Oncology Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Karasek
authors.affiliation: Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.|Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.|International Clinical Research Center, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Renata
authors.initials: R
authors.lastname: Veselska
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism; D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism*; D000368:Aged; D014408:Biomarkers, Tumor; D051927:CD24 Antigen / Q000378:metabolism; D002478:Cells, Cultured; D000071858:Epithelial Cell Adhesion Molecule / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D064231:Nestin / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D000071916:AC133 Antigen; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D018960:Hyaluronan Receptors; C577484:NES protein, human; D064231:Nestin; C000606023:PROM1 protein, human