NANOG overexpression and its correlation with stem cell and differentiation markers in meningiomas of different WHO grades

• Published in: Molecular carcinogenesis Vol. 56; no. 8; pp. 1953 - 1964
• Main Authors: Freitag, Diana, McLean, Aaron Lawson, Simon, Michèle, Koch, Arend, Grube, Susanne, Walter, Jan, Kalff, Rolf, Ewald, Christian
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.08.2017
• Subjects: Antigens, Differentiation - analysis; Antigens, Differentiation - genetics; Brain cancer; Cancer; CD44 antigen; Fluorescence; Fluorescence microscopy; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Immunofluorescence; KLF4 protein; Localization; Meningeal Neoplasms - genetics; Meningeal Neoplasms - pathology; Meningioma; Meningioma - genetics; Meningioma - pathology; Microscopy; Msi1 protein; NANOG; Nanog Homeobox Protein - analysis; Nanog Homeobox Protein - genetics; Neoplastic Stem Cells - cytology; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Nestin; Notch1 protein; Oct-4 protein; p53 Protein; Pluripotency; Stem cells; Transcription factors; Tumorigenesis; Tumors; Up-Regulation; meningioma; NANOG; pluripotency; gene expression
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.22653

NANOG, as a key regulator of pluripotency and acting synergistically with other factors, has been described as a crucial transcription factor in various types of cancer. In meningiomas the expression of this marker has not yet been described. With our study, we aimed to identify and localize NANOG and other possible markers of pluripotency, stem cell properties and differentiation in meningioma tissue, to elucidate a possible effect on tumorigenesis. The gene expression levels of NANOG (NANOG1 and NANOGP8), SOX2, OCT4, KLF4, ABCG2, CMYC, MSI1, CD44, NOTCH1, NES, SALL4B, TP53, and EPAS1 were quantitatively examined using RT‐qPCR in 33 surgical specimens of low‐ (WHO grade I) as well as in high‐grade (WHO grade II/III) meningiomas with dural tissue as reference. Immunofluorescence co‐localization analysis following confocal fluorescence microscopy for NANOG, OCT4, SOX2, Nestin, KI‐67, and CD44 was also performed. There was a significant overexpression of NANOG, MSI1, and EPAS1 and a downregulation of NES in all examined tumors. Subgroup analysis (WHO grade I versus grade II/III) revealed differences in the expression of NANOG, CD44, and MSI1. We found 1% NANOG‐positive (NANOG+) cells in low‐grade and 2% in grade II/III meningiomas co‐expressing the other mentioned markers in various compositions. In particular, NANOG+ cells expressing SOX2 and OCT4 were successfully identified (26% low‐grade versus 20% high‐grade). Our data reveal an overexpression of NANOG and other markers of pluripotency and stemness in meningiomas. Such potentially pluripotent “stem cell‐like” cells may have an impact on tumorigenesis and progression in human meningiomas.