title: Cancer stem cell markers in pediatric sarcomas: Sox2 is associated with tumorigenicity in immunodeficient mice.
abstract: The three most frequent pediatric sarcomas, i.e., Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma, were examined in this study: three cell lines derived from three primary tumor samples were analyzed from each of these tumor types. Detailed comparative analysis of the expression of three putative cancer stem cell markers related to sarcomas-ABCG2, CD133, and nestin-was performed on both primary tumor tissues and corresponding cell lines. The obtained results showed that the frequency of ABCG2-positive and CD133-positive cells was predominantly increased in the respective cell lines but that the high levels of nestin expression were reduced in both osteosarcomas and rhabdomyosarcomas under in vitro conditions. These findings suggest the selection advantage of cells expressing ABCG2 or CD133, but the functional tests in NOD/SCID gamma mice did not confirm the tumorigenic potential of cells harboring this phenotype. Subsequent analysis of the expression of common stem cell markers revealed an evident relationship between the expression of the transcription factor Sox2 and the tumorigenicity of the cell lines in immunodeficient mice: the Sox2 levels were highest in the two cell lines that were demonstrated as tumorigenic. Furthermore, Sox2-positive cells were found in the respective primary tumors and all xenograft tumors showed apparent accumulation of these cells. All of these findings support our conclusion that regardless of the expression of ABCG2, CD133 and nestin, only cells displaying increased Sox2 expression are directly involved in tumor initiation and growth; therefore, these cells fit the definition of the cancer stem cell phenotype.
authors.affiliation: Department of Experimental Biology, School of Science, Masaryk University, Brno, Czech Republic.|Department of Pediatric Oncology, University Hospital Brno and School of Medicine, Masaryk University, Brno, Czech Republic.|International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Skoda
authors.affiliation: Department of Experimental Biology, School of Science, Masaryk University, Brno, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Nunukova
authors.affiliation: Department of Experimental Biology, School of Science, Masaryk University, Brno, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Loja
authors.affiliation: 1st Institute of Pathologic Anatomy, St. Anne's University Hospital and School of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Iva
authors.initials: I
authors.lastname: Zambo
authors.affiliation: Department of Experimental Biology, School of Science, Masaryk University, Brno, Czech Republic.|Department of Pediatric Oncology, University Hospital Brno and School of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Jakub
authors.initials: J
authors.lastname: Neradil
authors.affiliation: Department of Pediatric Oncology, University Hospital Brno and School of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Mudry
authors.affiliation: Department of Pediatric Oncology, University Hospital Brno and School of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Karel
authors.initials: K
authors.lastname: Zitterbart
authors.affiliation: 1st Institute of Pathologic Anatomy, St. Anne's University Hospital and School of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Marketa
authors.initials: M
authors.lastname: Hermanova
authors.affiliation: Department of Histology and Embryology, School of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Ales
authors.initials: A
authors.lastname: Hampl
authors.affiliation: Department of Pediatric Oncology, University Hospital Brno and School of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Sterba
authors.affiliation: Department of Experimental Biology, School of Science, Masaryk University, Brno, Czech Republic. veselska@sci.muni.cz.|Department of Pediatric Oncology, University Hospital Brno and School of Medicine, Masaryk University, Brno, Czech Republic. veselska@sci.muni.cz.|International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic. veselska@sci.muni.cz.
authors.forename: Renata
authors.initials: R
authors.lastname: Veselska
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D064231:Nestin / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D012208:Rhabdomyosarcoma / Q000378:metabolism / Q000473:pathology; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D012509:Sarcoma / Q000378:metabolism* / Q000473:pathology*
chemical_list: C116614:ABCG2 protein, human; D000071916:AC133 Antigen; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D064231:Nestin; C000606023:PROM1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
keywords: Cancer stem cells; Markers; Pediatric sarcomas; Sox2; Tumorigenicity