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CD133+ niches and single cells in glioblastoma have different phenotypes

Journal of Neuro-Oncology volume 104, pages 129–143 (2011)Cite this article

Abstract

Putative CD133+ brain tumor stem cells have been shown to be located in niches and as single cells. This is the first study providing insight into the different phenotypes of CD133+ cells in glioblastoma according to localization. Paraffin sections were stained by double immunofluorescence with CD133 and the candidate stem cell markers Sox2, Bmi-1, EGFR, podoplanin and nestin, the proliferation marker Ki67 and the endothelial cell markers CD31, CD34, and VWF. Cell counting showed that the CD133+ cells in the niches had a significantly higher expression of Sox2, EGFR and nestin compared to CD133+ single cells, but only a 3% Ki67 labeling index versus 14% found for CD133+ single cells. Only low endothelial cell marker expression was found in the niches or the CD133− tumor areas, while 43% CD133+/CD31+ and 25% CD133+/CD34+ single cells were found. CD133+ blood vessels within CD133+ niches were less proliferative and more often Bmi-1+ than CD133+ blood vessels outside niches. In conclusion, different CD133+ cell phenotypes exist according to the in situ localization, and also the phenotype of CD133+ blood vessels vary according to the localization. CD133+ niches contain stem-like cells with a lower proliferation index than CD133+ single cells, which have an endothelial differentiation profile suggesting a role in angiogenesis.

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Acknowledgments

The excellent laboratory work of Helle Wohlleben and Tanja Dreehsen is gratefully acknowledged. We are grateful to Ole Nielsen for critical comments and suggestions regarding the immunohistochemical and immunofluorescence protocols. This work was supported by the Danish Cancer Society, Danish Medical Research Council, Danish Cancer Research Foundation, Johs. Clemmesen’s Research Foundation, Hørslev Foundation, Merchant M. Kristian Kjær and wife Margrethe Kjær born la Cour-Holmen’s Foundation, The Harboe Foundation, Karen A. Tolstrup’s Foundation, Kathrine and Vigo Skovgaard’s Foundation, Eva and Henry Frænkel’s Memorial Foundation, and Merchant M. Brogaard and wife’s Memorial Foundation.

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  1. Department of Pathology, Odense University Hospital, Winsløwparken 15, 5000, Odense C, Denmark

    Karina Christensen, Henrik Daa Schrøder & Bjarne Winther Kristensen

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  1. Karina Christensen
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  2. Henrik Daa Schrøder
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Christensen, K., Schrøder, H.D. & Kristensen, B.W. CD133+ niches and single cells in glioblastoma have different phenotypes. J Neurooncol 104, 129–143 (2011). https://doi.org/10.1007/s11060-010-0488-y

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Keywords

  • CD133
  • Glioblastoma
  • Niche
  • Tumor stem cells