Abstract
Although CD90 has been identified as a marker for various kinds of stem cells including liver cancer stem cells (CSCs) that are responsible for tumorigenesis, the potential role of CD90 as a marker for CSCs in gliomas has not been characterized. To address the issue, we investigated the expression of CD90 in tissue microarrays containing 15 glioblastoma multiformes (GBMs), 19 WHO grade III astrocytomas, 13 WHO grade II astrocytomas, 3 WHO grade I astrocytomas and 8 normal brain tissues. Immunohistochemical analysis showed that CD90 was expressed at a medium to high level in all tested high-grade gliomas (grade III and GBM) whereas it was barely detectable in low-grade gliomas (grade I and grade II) and normal brains. Double immunofluorescence staining for CD90 and CD133 in GBM tissues revealed that CD133(+) CSCs are a subpopulation of CD90(+) cells in GBMs in vivo. Flow cytometry analysis of the expression of CD90 and CD133 in GBM-derived stem-like neurospheres further confirmed the conclusion in vitro. The expression levels of both CD90 and CD133 were reduced along with the loss of stem cells after differentiation. Furthermore, the limiting dilution assay demonstrated that the sphere formation ability was comparable between the CD90(+)/CD133(+) and the CD90(+)/CD133(-) populations of GBM neurospheres, which is much higher than that of the CD90(-)/CD133(-) population. We also performed double staining for CD90 and a vascular endothelial cell marker CD31 in tissue microarrays which revealed that the CD90(+) cells were clustered around the tumor vasculatures in high-grade glioma tissues. These findings suggest that CD90 is not only a potential prognostic marker for high-grade gliomas but also a marker for CSCs within gliomas, and it resides within endothelial niche and may also play a critical role in the generation of tumor vasculatures via differentiation into endothelial cells.
Highlights
From the ‡Department of Surgery, University of Michigan Medical Center Ann Arbor, Michigan 48109; §Department of Neurosurgery, University of Michigan Medical Center, Ann Arbor, Michigan 48109; ¶Department of Cell and Developmental Biology, University of Michigan Medical Center, Ann Arbor, Michigan 48109; ʈDepartments of Neurological Surgery, Johns Hopkins University, Baltimore, Maryland 21205; **Department of Neurosurgery, Istituto Nazionale Neurologico C
We applied tissue microarrays to analyze the expression of CD90 in different grades of glioma tissues and found that the CD90 levels in high-grade gliomas (WHO grade III and IV) were significantly higher than in low-grade gliomas (WHO grade I and II) and normal brains (Fig. 1 and Fig. 2)
Because the expression level of CD90 is dramatically increased in glioblastoma multiformes (GBMs) compared with low-grade gliomas, CD90 can be a new marker of these cancer stem cells (CSCs) within GBM tissues
Summary
From the ‡Department of Surgery, University of Michigan Medical Center Ann Arbor, Michigan 48109; §Department of Neurosurgery, University of Michigan Medical Center, Ann Arbor, Michigan 48109; ¶Department of Cell and Developmental Biology, University of Michigan Medical Center, Ann Arbor, Michigan 48109; ʈDepartments of Neurological Surgery, Johns Hopkins University, Baltimore, Maryland 21205; **Department of Neurosurgery, Istituto Nazionale Neurologico C. These results suggest that both CD90 and CD133 levels were decreased along with the loss of stem-like cells, and CD90 may represent a new marker for CSCs in GBM.
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