Expression of Embryonic Stem Cell Markers on the Microvessels of WHO Grade I Meningioma

Abstract

Aim: The presence of cells within meningioma (MG) that express embryonic stem cell (ESC) markers has been previously reported. However, the precise location of these cells has yet to be determined.Methods: 3,3-Diaminobenzidine (DAB) immunohistochemical (IHC) staining was performed on 11 WHO grade I MG tissue samples for the expression of the ESC markers OCT4, NANOG, SOX2, KLF4 and c-MYC. Immunofluorescence (IF) IHC staining was performed to investigate the localization of each of these ESC markers. NanoString and colorimetric in situ hybridization (CISH) mRNA expression analyses were performed on six snap-frozen MG tissue samples to confirm transcriptional activation of these proteins, respectively.Results: DAB IHC staining demonstrated expression of OCT4, NANOG, SOX2, KLF4, and c-MYC within all 11 MG tissue samples. IF IHC staining demonstrated the expression of the ESC markers OCT4, NANOG, SOX2, KLF4, and c-MYC on both the endothelial and pericyte layers of the microvessels. NanoString and CISH mRNA analyses confirmed transcription activation of these ESC markers.Conclusion: This novel finding of the expression of all aforementioned ESC markers in WHO grade I MG infers the presence of a putative stem cells population which may give rise to MG.

Expression of Cathepsins B, D, and G in WHO Grade I Meningioma

“…To determine whether each cathepsin was expressed by the putative TSC population on the microvessels that express the ESC markers we have previously reported in WHO grade I MG (17), we co-stained each cathepsin with the pericyte marker, SMA (37). Cathepsin B (Figure 3A, red) and cathepsin D (Figure 3B, red) were illustrated on both the endothelium as well as the outer pericyte layer.…”

“…This study demonstrated the expression of cathepsins B, D, and G in WHO grade I MG. Cathepsin B and cathepsin D were enzymatically active and were demonstrated on the putative TSC population of the endothelial and pericyte layers of the microvessels (17), which expresses components of the RAS (18). NanoString mRNA expression and WB analyses demonstrated low levels of mRNA transcripts and protein expression of cathepsin G, respectively.…”

“…WHO grade I MG tissue samples from one male and nine female patients, age 36–85 (mean, 61.2) years included in our previous studies (17, 18), were sourced from the Gillies McIndoe Research Institute Tissue Bank for this study. Study approval was granted by the Central Regional Health and Disability Ethics Committee (Ref.…”

“…Takahashi et al (16) were the first to elucidate expression of ESC markers OCT4, SALL4, NANOG, SOX2, c-MYC, and KLF4, with the ability to induce and maintain pluripotency in addition to a deregulated capacity for renewal in induced pluripotent stem cells. We have recently demonstrated the presence of an ESC-like population which expresses OCT4, NANOG, SOX2, KLF4, and c-MYC on both the endothelial and pericyte layers of the microvessels in World Health Organization (WHO) grade I MG (17). This ESC-like population expresses components of the renin-angiotensin system (RAS): pro(renin) receptor (PRR), angiotensin converting enzyme (ACE), angiotensin II receptor 1 (ATIIR1), and angiotensin II receptor 2 (ATIIR2) in the microvessels in this tumor (18).…”

“…The expression of cathepsin B by the stem cell niche on the microvessels in GB has been reported recently (31), with this staining pattern being a negative prognostic factor (32). This study was aimed at investigating the expression of cathepsins B, D, and G in WHO grade I MG, in relation to the putative TSC population we have previously identified (17).…”