title: Expression profiling of stem cell signaling alters with spheroid formation in CD133high/CD44highprostate cancer stem cells.
abstract: Cancer stem cells (CSC) isolated from multiple tumor types differentiatein vivoandin vitrowhen cultured in serum; however, the factors responsible for their differentiation have not yet been identified. The first aim of the present study was to identify CD133high/CD44highDU145 prostate CSCs and compare their profiles with non-CSCs as bulk counterparts of the population. Subsequently, the two populations continued to be three-dimensional multicellular spheroids. Differentiation was then investigated with stem cell-related genomic characteristics. Polymerase chain reaction array analyses of cell cycle regulation, embryonic and mesenchymal cell lineage-related markers, and telomerase reverse transcriptase (TERT) andNotchsignaling were performed. Immunohistochemistry ofCD117,Notch1,Jagged1,Delta1,Sox2,c-Myc,Oct4,KLF4,CD90andSSEA1were determined in CSC and non-CSC monolayer and spheroid subcultures. Significant gene alterations were observed in the CD133high/CD44highpopulation when cultured as a monolayer and continued as spheroid. In this group, marked gene upregulation was determined incollagen type 9 α1,Islet1andcyclin D2. Jagged1,Delta-like 3andNotch1were respectively upregulated genes in the Notch signaling pathway. According to immunoreactivity, the staining density ofJagged1,Sox2,Oct4andKlf-4increased significantly in CSC spheroids. Isolated CSCs alter their cellular characterization over the course of time and exhibit a differentiation profile while maintaining their former surface antigens at a level of transcription or translation. The current study suggested that this differentiation process may be a mechanism responsible for the malignant process and tumor growth.
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Ege University, Bornova, Izmir 35100, Turkey.
authors.forename: Gulperi
authors.initials: G
authors.lastname: Oktem
authors.affiliation: Department of Histology and Embryology, Istanbul Medical Faculty, Istanbul University, Capa, Istanbul 34098, Turkey.
authors.forename: Ayhan
authors.initials: A
authors.lastname: Bilir
authors.affiliation: Department of Medical Oncology, Faculty of Medicine, Ege University, Bornova, Izmir 35100, Turkey.
authors.forename: Ruchan
authors.initials: R
authors.lastname: Uslu
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Manisa 45030, Turkey.
authors.forename: Sevinc V
authors.initials: SV
authors.lastname: Inan
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Ege University, Bornova, Izmir 35100, Turkey.
authors.forename: Sirin B
authors.initials: SB
authors.lastname: Demiray
authors.affiliation: Department of Biology, Faculty of Science and Art, Celal Bayar University, Manisa 45030, Turkey.
authors.forename: Harika
authors.initials: H
authors.lastname: Atmaca
authors.affiliation: Zeynep Kamil Gynecology and Maternity Training and Research Hospital, Istanbul 34668, Turkey.
authors.forename: Sule
authors.initials: S
authors.lastname: Ayla
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Dokuz Eylul University, Bornova, Izmir 35340, Turkey.
authors.forename: Ogun
authors.initials: O
authors.lastname: Sercan
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Ege University, Bornova, Izmir 35100, Turkey.
authors.forename: Aysegul
authors.initials: A
authors.lastname: Uysal
keywords: cancer stem cell; prostate cancer; spheroid; stem cell-related genes