Article
CD133 positive “Cancer stem cells” in gliomas of different grades
CD133-positive "cancer stem cells" in Gliomen verschiedener Grade
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Published: | May 8, 2006 |
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Objective: Within glioblastoma multiforme (GBM) specimens, CD133 positive cells with ability for self renewal and tumor generation could be isolated suggesting the presence of “cancer stem cells” (CSC) in GBM. Aim of this study was (i) to assess the presence of CD133+ cells in gliomas grade II, III and IV and (ii) to investigate the differentiation potential of these cells.
Methods: Samples of GBM (n=10), glioma WHO °III (n=7) and glioma WHO °II (n=6) were investigated immunohistochemically using the antibody AC133/1+2, which binds to two different epitopes of CD133, and Musashi-1, an established stem cell marker. Additionally, CD133 expression was assessed by ELISA. CD133+ cells were isolated from freshly resected gliomas grade II, III and IV (each n=3) using a modified magnetic bead protocol. These cells were stained for Musashi-1 and cultured using different media. Differentiation of cultured cells was assessed immunohistochemically using anti-GFAP, -NSE, -CD31, -CD105, -VE cadherin and -CD133.
Results: CD133 positive cells could be detected in 5/6 gliomas WHO °II, 6/7 gliomas WHO°III and 10/10 GBM. These cells were found arranged in clusters, mostly associated to intratumoral vessels, rarely located diffusely within the tumor parenchyma. CD133 expression correlated with WHO grade: 1-5% of cells in gliomas WHO °II, 5-10% of cells in gliomas WHO °III, and 10-15% of cells in GBM stained positive for CD133. ELISA data confirmed the correlation with tumor grade. CD133+ cells that have been isolated from specimens of all tumor grades stained positive for Musashi-1. Under different culture conditions, rapid proliferation of CD133+ cells occurred. After several passages, cells lost CD133 expression and became positive for GFAP, NSE or CD31/CD105/VE cadherin.
Conclusions: This study represents the first documentation for the presence of pluripotent, highly proliferative CD133+ CSC in low grade gliomas, which are able to differentiate into cells expressing glial, neuronal or endothelial markers. The presence of CSC in high grade gliomas could be confirmed, showing a higher proportion than in low grade gliomas. The role of these cells during stepwise glioma progression still has to be evaluated.