Article

Identification of A2B5+CD133- tumor-initiating cells in adult human gliomas

Department of Neurological Surgery, The Neurological Institute, Columbia University, New York, New York 10032, USA.
Neurosurgery (Impact Factor: 3.62). 03/2008; 62(2):505-14; discussion 514-5. DOI: 10.1227/01.neu.0000316019.28421.95
Source: PubMed

ABSTRACT

Several studies have shown that human gliomas contain a small population of cells with stem cell-like features. It has been proposed that these "cancer stem cells" may be uniquely responsible for glioma formation and recurrence. However, human gliomas also contain an abundance of cells that closely resemble more differentiated glial progenitors. Animal model studies have shown that these cells also possess the capacity to form malignant gliomas.
To investigate the contributions of stem-like and progenitor-like cells in human gliomas, we used flow cytometry to characterize the expression of a cancer stem cell marker (CD133) and a glial progenitor marker (A2B5) in 25 tumors. We found that human gliomas consistently express A2B5 in a large percentage of cells (61.7 +/- 3.8%, standard error of the mean). In contrast, CD133 expression was less abundant and less consistent (14.8 +/- 3.6%, standard error of the mean), with several glioblastomas containing very few or no detectable CD133+ cells. When present, the CD133+ population was almost entirely contained within the A2B5+ population. Thus, most gliomas could be divided into three distinct populations on the basis of these markers (A2B5+CD133+, A2B5+CD133-, and A2B5-CD133-). To test the tumorigenic potential of these populations, we separated cells from six tumors by fluorescence-activated cell sorting and reinjected them into nude rats.
We found that the capacity for these different populations to form tumors varied depending on the human tumor specimen from which they were isolated. Of the six human gliomas tested, four contained A2B5+/CD133- cells that formed tumors when transplanted into nude rats, three contained A2B5+/CD133+ cells that formed tumors, and only one glioma contained A2B5-/CD133- cells with the capacity to form tumors.
Together, these results demonstrate that human gliomas contain multiple populations of cells with the capacity to form tumors and specifically identify a population of tumorigenic A2B5+ cells that are phenotypically distinct from CD133+ cells.

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    • "And third, the lack of systematic clinical characterization of the tumors from which the current GC lines derive makes it impossible to correlate findings with these models to patient parameters. There is ample evidence that a minor subset of GBM cells (GCs), denoted glioblastoma stem cells (GSCs) are likely responsible for relapse because they possess a unique capacity for growth and progression (Beier et al., 2007; Galli et al., 2004; Lathia et al., 2010; Ogden et al., 2008; Singh et al., 2004; Son et al., 2009) and are particularly resistant to therapy (Bao et al., 2006; Bleau et al., 2009; Chen et al., 2012). Research designed to improve GBM culture conditions has shown that GSCs can be readily cultured as spheres, utilizing the same conditions as for normal neural stem cells (Hemmati et al., 2003; Ignatova et al., 2002; Singh et al., 2003). "
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    ABSTRACT: Glioblastoma (GBM) is the most frequent and malignant form of primary brain tumor. GBM is essentially incurable and its resistance to therapy is attributed to a subpopulation of cells called glioma stem cells (GSCs). To meet the present shortage of relevant GBM cell (GC) lines we developed a library of annotated and validated cell lines derived from surgical samples of GBM patients, maintained under conditions to preserve GSC characteristics. This collection, which we call the Human Glioblastoma Cell Culture (HGCC) resource, consists of a biobank of 48 GC lines and an associated database containing high-resolution molecular data. We demonstrate that the HGCC lines are tumorigenic, harbor genomic lesions characteristic of GBMs, and represent all four transcriptional subtypes. The HGCC panel provides an open resource for in vitro and in vivo modeling of a large part of GBM diversity useful to both basic and translational GBM research.
    Full-text · Article · Aug 2015 · EBioMedicine
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    • "Nevertheless, although sub-populations of tumorigenic cancer cells with self-renewal and differentiation capacities have been characterized in leukaemia and several solid tumors, the cancer stem cell concept remains controversial [14] [15] [16] [17] [18]. Indeed, recent data have raised concerns about the use of Hoechst dye exclusion to define cancer stem cells [19] [20] [21] [22] [23], and CD133 negative cells have recently been described as tumorigenic in brain and colon tumors [24] [25] [26]. "

    Full-text · Dataset · Feb 2015
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    • "Nevertheless, although sub-populations of tumorigenic cancer cells with self-renewal and differentiation capacities have been characterized in leukaemia and several solid tumors, the cancer stem cell concept remains controversial [14] [15] [16] [17] [18]. Indeed, recent data have raised concerns about the use of Hoechst dye exclusion to define cancer stem cells [19] [20] [21] [22] [23], and CD133 negative cells have recently been described as tumorigenic in brain and colon tumors [24] [25] [26]. "

    Full-text · Dataset · Feb 2015
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