Expression of the stem cell marker CD133 in recurrent glioblastoma and its value for prognosis |
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| Authors: | Roberto Pallini MD Nicola Montano MD Cristiana Mollinari PhD Mauro Biffoni PhD Tonia Cenci PhD Francesco Pierconti MD Maurizio Martini MD Ruggero De Maria MD Luigi Maria Larocca MD |
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| Institution: | 1. Institute of Neurosurgery, Catholic University School of Medicine, Rome, ItalyFax: (011) 39 06 3051 343The first 2 authors contributed equally to this work.;2. Institute of Neurosurgery, Catholic University School of Medicine, Rome, Italy;3. Department of Cell Biology and Neuroscience, Superior Health Institute, Rome, Italy;4. Institute of Neurobiology and Molecular Medicine, National Research Council, Rome, Italy;5. Department of Hematology, Oncology, and Molecular Medicine, Superior Health Institute, Rome, Italy;6. Institute of Pathological Anatomy, Catholic University School of Medicine, Rome, Italy |
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| Abstract: | BACKGROUND: Experimental data suggest that glioblastoma cells expressing the stem cell marker CD133 play a major role in radiochemoresistance and tumor aggressiveness. To date, however, there is no clinical evidence that the fraction of CD133‐positive cells in glioblastoma that recurs after radiochemotherapy may be relevant for prognosis. METHODS: The authors used immunohistochemistry to assess CD133 expression in 37 paired glioblastoma samples, including 1 primary tumor sample and 1 recurrent tumor sample, after patients received adjuvant radiochemotherapy. To assess the actual composition of the CD133‐positive glioblastoma cell population, fluorescence‐associated cell sorting (FACS) analysis was used to sort CD133‐positive/CD45‐negative cells that were assayed for tumor‐specific chromosomal aberrations using interphase fluorescence in situ hybridization. To rule out endothelial precursor cells, CD133‐positive fractions also were assayed with anti‐CD34 by FACS. RESULTS: In recurrent glioblastomas, the percentage of CD133‐positive cells was increased by 4.6‐fold compared with the percentage in primary glioblastomas, although, in some tumors, it increased up to 10‐fold and 20‐fold. Unexpectedly, the increase in CD133 expression was associated significantly with longer survival after tumor recurrence. An analysis of tumor‐specific chromosomal aberrations and in vivo studies revealed that the CD133‐positive cell compartment of recurrent glioblastoma was composed of both cancer stem cells and nontumor neural stem cells. The latter cells represented from 20% to 60% of the CD133‐positive cell population, and their relative percentage favorably affected the survival of patients with recurrent glioblastoma. Endothelial CD133‐positive/CD34‐positive precursors did not contribute to the CD133‐positive cell population. CONCLUSIONS: The authors hypothesized that, similar to the phenomenon described in glioblastoma models, neural stem/progenitor cells that are recruited by the tumor from surrounding brain may exert an antitumorigenic effect. Cancer 2011. © 2010 American Cancer Society. |
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| Keywords: | glioblastoma cancer stem cells CD133 tumor recurrence |
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