Expression of stem cell markers in human astrocytomas of different WHO grades

Abstract

According to new hypotheses astrocytomas/gliomas either arise from or attract neural stem cells. Biological markers, particularly antigenic markers, have played a significant role for the characterization of these tumour stem cells (TSCc). Because these studies have been performed with single experimental samples mostly from gliomas, we investigated the expression of the stem cell markers CD133/Prominin, Nestin, Sox-2, Musashi-1, CXCR4, Flt-4/VEGFR-3 and CD105/Endoglin in 72 astrocytomas of different WHO-grades and compared it to normal adult human brain. Expression of their mRNA was quantified by quantitative RT-PCR, of their protein by counting immunopositive cells. In contrast to normal brain, tumour samples showed a high variability for the expression of all markers. However, their mean expression was significantly increased in astrocytomas, but this depended on the WHO grade only for CD133, Nestin, Sox-2 and Musashi-1. Confocal microscopy revealed that these markers mostly could be co-stained with glial fibrillary acidic protein, a marker for astoglial cells, but less frequently with the proliferation marker Ki-67/MIB-1. These markers sometimes, but not necessarily could be co-stained with each other in complex patterns. Our results show that most astrocytomas contain considerable portions of cells expressing stem cell markers. It appears that some of these cells originate from tumour genesis (supporting the stem cell hypothesis) while others are attracted by the tumours. Further functional markers are required to differentiate these TSC-types.

Identification of OLIG2 as the most specific glioblastoma stem cell marker starting from comparative analysis of data from similar DNA chip microarray platforms

“…Many markers potentially specific for GSCs have been proposed such as A2B5 cell surface ganglioside epitope (A2B5) [26,27], aldehyde dehydrogenase (ALDH) [28], BMI1 polycomb ring finger oncogene (BMI1) [29,30], fucosyltransferase 4 (FUT4) (CD15) [31], Thy-1 cell surface antigen (Thy-1) (CD90) [32], prominin-1 (PROM1) (CD133) [5,6], chemokine (C-X-C motif) receptor 4 (CXCR4) [33], inhibitor of DNA binding 1 (ID1) [34], integrin α6 (ITGA6) [35], L1 cell adhesion molecule (L1CAM) [36], maternal embryonic leucine zipper kinase (MELK) [37], musashi-1 (msi1) [38], nestin (NES) [38][39][40], octamer-binding transcription factor 4 (OCT4) [41], OLIG2 [42] and SOX2 [38,[43][44][45]. Among these, much attention has been given to CD133, which is currently used to identify and isolate GSCs [40,43,[46][47][48][49][50].…”

“…Among these, much attention has been given to CD133, which is currently used to identify and isolate GSCs [40,43,[46][47][48][49][50]. Despite the fact that this is the most widely used antigen for enrichment of GSCs, there are several arguments to suggest the existence of CD133-negative GSCs: CD133 is not detectable in many fresh GBM specimens [14,31,51], and some studies revealed CD133-negative GBM cultures with the ability to self-renew and to form tumours in xenotransplantation assays [14,51,52].…”

Expression of neural stem cell markers in malignant rhabdoid tumor cell lines

“…Nestin has been detected in brain tumors such as pilocytic astrocytomas and malignant gliomas including glioblastoma multiforme (27,28,52,53). Our results showed that STM91-01, TTC549 and TTC1240 expressed nestin, which was detected by RT-PCR and Western blotting.…”

“…Msi-1 is an RNA binding protein which is preferentially expressed in stem-cells, functions as a translational repressor (56)(57)(58), and is widely used as a molecular marker to identify stem cells in embryos and adult tissues (26)(27)(28)(29). In our study, Msi-1 was expressed in five MRT cell lines except TTC642, which originated from a neck mass.…”

“…In recent years, the concept of CSC involvement in tumorigenesis has attracted the attention of many researchers. Previous studies have shown that NSC acting as CSC is recognized in CNS (24)(25)(26)(27)(28)(29). In the present study, we examined the expression of NSC markers such as CD133, nestin and Msi-1 before and after 4-HPR induced differentiation in MRT cell lines to elucidate the cytological characteristics of MRT cells that are considered to derive from neuroectodermal origin (8,9,12).…”