CD90 is identified as a candidate marker for cancer stem cells in primary high-grade gliomas using tissue microarrays.

Jintang He, Yashu Liu, Thant Zhu, Jianhui Zhu, Francesco Dimeco, Angelo L. Vescovi, Jason A. Heth, Karin M. Muraszko, Xing Fan, David M. Lubman

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalMolecular and Cellular Proteomics
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 2012

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Neoplastic Stem Cells
Glioblastoma
Microarrays
Stem cells
Glioma
Tissue
Astrocytoma
Endothelial cells
Tumors
Brain
Stem Cells
Endothelial Cells
Staining and Labeling
Flow cytometry
Liver Neoplasms
Liver
Population
Dilution
Fluorescent Antibody Technique
Cell Differentiation

ASJC Scopus subject areas

  • Medicine(all)

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CD90 is identified as a candidate marker for cancer stem cells in primary high-grade gliomas using tissue microarrays. / He, Jintang; Liu, Yashu; Zhu, Thant; Zhu, Jianhui; Dimeco, Francesco; Vescovi, Angelo L.; Heth, Jason A.; Muraszko, Karin M.; Fan, Xing; Lubman, David M.

In: Molecular and Cellular Proteomics, Vol. 11, No. 6, 06.2012.

Research output: Contribution to journalArticle

He, Jintang ; Liu, Yashu ; Zhu, Thant ; Zhu, Jianhui ; Dimeco, Francesco ; Vescovi, Angelo L. ; Heth, Jason A. ; Muraszko, Karin M. ; Fan, Xing ; Lubman, David M. / CD90 is identified as a candidate marker for cancer stem cells in primary high-grade gliomas using tissue microarrays. In: Molecular and Cellular Proteomics. 2012 ; Vol. 11, No. 6.
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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.",
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AU - Zhu, Thant

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AU - Dimeco, Francesco

AU - Vescovi, Angelo L.

AU - Heth, Jason A.

AU - Muraszko, Karin M.

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