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  • Glioblastoma Multiforme: Putative Stem Cell Hierachy

    Final Number:

    Agadha Wickremesekera, Helen D Brasch, Amy Bradshaw, Kirsty Mayall, Alice M Chibnall, Paul F Davis, Swee T Tan, Tinte Itinteang

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2016 Annual Meeting

    Introduction: Glioblastoma Multiforme (GBM) the most aggressive form of brain glioma, is associated with a median survival of 25 months. Cancer stem cells (CSCs) have been reported to express stem cell markers and have been proposed to be the origin of many cancers, including GBM(1). This study was aimed at characterizing the CSC population within GBM tissue for the CSC markers SALL4, OCT4, SOX2, pSTAT3 and NANOG (2, 3). Furthermore we have researched some of the properties of the neuro-spheres derived from freshly acquired surgical GBM samples and investigated them for the expression of stem cell markers.

    Methods: Immunohistochemistry was performed on seven GBM samples for the stem cell markers SALL4, OCT4, SOX2, NANOG and pSTAT3. Nanostring mRNA analysis was performed on five of the IHC cohort for the transcriptional analyses of the same stem cell markers. Cells from three surgically excised samples from the IHC cohort were grown in culture and stained for alkaline phosphatase (AP) activity, which has been associated with cancer stem cells.

    Results: IHC demonstrated a significant number of cells from GBM expressed SOX2 and pSTAT3. A subset of these also expressed OCT4, SALL4 and NANOG. Nanostring analysis demonstrated the expression of mRNA transcripts for these same markers. Cultures of GBM tissue revealed the growth of neuro-spheres which expressed AP.

    Conclusions: The expression of the stem cell markers within GBM highlights the identification of putative presence of CSCs in this tumor. The relative abundance of SOX2 and pSTAT3 with less for SALL4, OCT4 and NANOG, suggests a hierarchy of CSCs within GBM with the latter population potentially being the most primitive CSC in GBM, and a potential target for the development of future safer treatment options for this tumor.

    Patient Care: The identification of a primitive cancer stem cell population in GBM for the development of future safer therapy.

    Learning Objectives: 1. The identification of cancer stem cells in GBM. 2. A putative hierarchy of the cancer stem cell population in GBM. 3. The novel identification of a putative target population for GBM.

    References: 1.Elsir T, Edqvist P, Carlson J, et al. A Study of embryonic stem cell-related proteins in human astrocytomas: identification of nanog as a predictor of survival. Int J Cancer. 2013; 134: 1123-1131. 2.Bradshaw A, Wickremesekera A, Tan ST, et al. Cancer stem cell hierarchy in glioblastoma multiforme. Front Surg. 2016 (Accepted). 3.Safa AR, Saadatzadeh MR, Cohen-Gadol AA, et al. Genes & Diseases. 2015; 2: 152-163.

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