Cancer Stem Cell Hierarchy in Glioblastoma Multiforme - PubMed (original) (raw)

Review

Cancer Stem Cell Hierarchy in Glioblastoma Multiforme

Amy Bradshaw et al. Front Surg. 2016.

Abstract

Glioblastoma multiforme (GBM), an aggressive tumor that typically exhibits treatment failure with high mortality rates, is associated with the presence of cancer stem cells (CSCs) within the tumor. CSCs possess the ability for perpetual self-renewal and proliferation, producing downstream progenitor cells that drive tumor growth. Studies of many cancer types have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is compounded further by the presence of multiple GBM and glioblastoma cancer stem cell subtypes, making investigation and establishment of a universal treatment difficult. This review examines the current knowledge on the CSC markers SALL4, OCT-4, SOX2, STAT3, NANOG, c-Myc, KLF4, CD133, CD44, nestin, and glial fibrillary acidic protein, specifically focusing on their use and validity in GBM research and how they may be utilized for investigations into GBM's cancer biology.

Keywords: cancer; cancer stem cell; glioblastoma multiforme; hierarchy; markers.

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Figures

Figure 1

Figure 1

CT (A) and T1 weighted MRI (B) scans with contrast of a patient with glioblastoma multiforme. Lesion indicated by red arrows.

Figure 2

Figure 2

Hematoxylin and eosin staining of a glioblastoma multiforme. (A) The interface between tumor cells and the area of necrosis. The necrotic area (arrows) show greatly reduced nuclear staining. (B) Proliferation of the endothelial cells (arrows) within a microvessel. (C) Palisading cells (arrows) around the necrotic area. Original magnification: 200×.

Figure 3

Figure 3

Current leading models of carcinogenesis. (A) The clonal evolution model hypothesizes that a normal cell (blue) within the organism undergoes a series of mutations to form a cancer cell (orange) that clonally expands and form the bulk of the tumor. Successful treatment must, therefore, eliminate all cancer cells. (B) The cancer stem cell (CSC) hierarchical model proposes that the origin of cancer being CSCs (red) that are pluripotent and self-renewing. They are highly tumorigenic with the ability to establish new tumors. CSCs divide asymmetrically to form new CSCs and progenitor (dark blue) cells that in turn give rise to differentiated cancer cells (light blue) that form the bulk of the tumor. These downstream cancer cells are low or non-tumorigenic. Adapted from Adams and Strasser (16).

Figure 4

Figure 4

The proposed hierarchy for neural stem cell differentiation. The system begins with the most primitive and multipotent cell and moves through stages of differentiation to the most restricted cell. Concept from Gage (24).

Figure 5

Figure 5

Current model for human hematopoiesis. All myeloid and lymphoid cells originate from a single hematopoietic stem cell (HSC). HSCs differentiate to form myeloid and lymphoid progenitor cells, which in turn differentiate to produce all of the diverse cells found in human blood. HSC, hematopoietic stem cell; Thr, thrombocytes; Ery, erythrocytes; MC, mast cell; Bas, basophil; Neu, neutrophil; Eos, eosinophil; Mono, monocyte; Macro, macrophage; B, B-cell; T, T-cell, NK, natural killer cell. Adapted from Bartis and Pongracz (86).

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