Expression profiling of stem cell signaling alters with spheroid formation in CD133(high)/CD44(high) prostate cancer stem cells


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ÖKTEM G. , Bilir A., Uslu R. , Inan S. V. , Demiray S. B. , Atmaca H., ...Daha Fazla

ONCOLOGY LETTERS, cilt.7, ss.2103-2109, 2014 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 7 Konu: 6
  • Basım Tarihi: 2014
  • Doi Numarası: 10.3892/ol.2014.1992
  • Dergi Adı: ONCOLOGY LETTERS
  • Sayfa Sayıları: ss.2103-2109

Özet

Cancer stem cells (CSC) isolated from multiple tumor types differentiate in vivo and in vitro when 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 CD133(high)/CD44(high) DU145 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) and Notch signaling were performed. Immunohistochemistry of CD117, Notch1, Jagged1, Delta1, Sox2, c-Myc, Oct4, KLF4, CD90 and SSEA1 were determined in CSC and non-CSC monolayer and spheroid subcultures. Significant gene alterations were observed in the CD133(high)/CD44(high) population when cultured as a monolayer and continued as spheroid. In this group, marked gene upregulation was determined in collagen type 9 a1, Islet1 and cyclin D2. Jagged1, Delta-like 3 and Notch1 were respectively upregulated genes in the Notch signaling pathway. According to immunoreactivity, the staining density of Jagged1, Sox2, Oct4 and Klf-4 increased 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.