18
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Contribution of the Microenvironmental Niche to Glioblastoma Heterogeneity

      review-article
      1 , 2 , * , 3 , 4
      BioMed Research International
      Hindawi

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Glioblastoma is the most aggressive cancer of the brain. The dismal prognosis is largely attributed to the heterogeneous nature of the tumor, which in addition to intrinsic molecular and genetic changes is also influenced by the microenvironmental niche in which the glioma cells reside. The cancer stem cells (CSCs) hypothesis suggests that all cancers arise from CSCs that possess the ability to self-renew and initiate tumor formation. CSCs reside in specialized niches where interaction with the microenvironment regulates their stem cell behavior. The reciprocal interaction between glioma stem cells (GSCs) and cells from the microenvironment, such as endothelial cells, immune cells, and other parenchymal cells, may also promote angiogenesis, invasion, proliferation, and stemness of the GSCs and be likely to have an underappreciated role in their responsiveness to therapy. This crosstalk may also promote molecular transition of GSCs. Hence the inherent plasticity of GSCs can be seen as an adaptive response, changing according to the signaling cue from the niche. Given the association of GSCs with tumor recurrence and treatment sensitivity, understanding this bidirectional crosstalk between GSCs and its niche may provide a framework to identify more effective therapeutic targets and improve treatment outcome.

          Related collections

          Most cited references128

          • Record: found
          • Abstract: found
          • Article: not found

          Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis.

          Previously undescribed prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class displaying neuronal lineage markers shows longer survival, while two tumor classes enriched for neural stem cell markers display equally short survival. Poor prognosis subclasses exhibit markers either of proliferation or of angiogenesis and mesenchyme. Upon recurrence, tumors frequently shift toward the mesenchymal subclass. Chromosomal locations of genes distinguishing tumor subclass parallel DNA copy number differences between subclasses. Functional relevance of tumor subtype molecular signatures is suggested by the ability of cell line signatures to predict neurosphere growth. A robust two-gene prognostic model utilizing PTEN and DLL3 expression suggests that Akt and Notch signaling are hallmarks of poor prognosis versus better prognosis gliomas, respectively.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found

            TIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis

            The p53 tumor-suppressor protein prevents cancer development through various mechanisms, including the induction of cell-cycle arrest, apoptosis, and the maintenance of genome stability. We have identified a p53-inducible gene named TIGAR (TP53-induced glycolysis and apoptosis regulator). TIGAR expression lowered fructose-2,6-bisphosphate levels in cells, resulting in an inhibition of glycolysis and an overall decrease in intracellular reactive oxygen species (ROS) levels. These functions of TIGAR correlated with an ability to protect cells from ROS-associated apoptosis, and consequently, knockdown of endogenous TIGAR expression sensitized cells to p53-induced death. Expression of TIGAR may therefore modulate the apoptotic response to p53, allowing survival in the face of mild or transient stress signals that may be reversed or repaired. The decrease of intracellular ROS levels in response to TIGAR may also play a role in the ability of p53 to protect from the accumulation of genomic damage.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Mesenchymal differentiation mediated by NF-κB promotes radiation resistance in glioblastoma.

              Despite extensive study, few therapeutic targets have been identified for glioblastoma (GBM). Here we show that patient-derived glioma sphere cultures (GSCs) that resemble either the proneural (PN) or mesenchymal (MES) transcriptomal subtypes differ significantly in their biological characteristics. Moreover, we found that a subset of the PN GSCs undergoes differentiation to a MES state in a TNF-α/NF-κB-dependent manner with an associated enrichment of CD44 subpopulations and radioresistant phenotypes. We present data to suggest that the tumor microenvironment cell types such as macrophages/microglia may play an integral role in this process. We further show that the MES signature, CD44 expression, and NF-κB activation correlate with poor radiation response and shorter survival in patients with GBM. Copyright © 2013 Elsevier Inc. All rights reserved.
                Bookmark

                Author and article information

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2017
                28 May 2017
                : 2017
                : 9634172
                Affiliations
                1Molecular Neurotherapeutics Laboratory, National Neuroscience Institute, Singapore
                2Department of Physiology, National University of Singapore, Singapore
                3National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore
                4Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore
                Author notes

                Academic Editor: Sara Piccirillo

                Author information
                http://orcid.org/0000-0002-2948-3726
                Article
                10.1155/2017/9634172
                5467280
                28630875
                277129d3-765f-4dcb-9ece-71dbe28358cc
                Copyright © 2017 Ivy A. W. Ho and Winston S. N. Shim.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 February 2017
                : 20 April 2017
                : 30 April 2017
                Funding
                Funded by: Singapore Ministry of Health's National Medical Research Council
                Award ID: NMRC/TCR/016-NNI/2-16
                Funded by: NCC Research Fund and Oncology ACP
                Funded by: National Neuroscience Institute
                Funded by: GOH Foundation Grant/Duke-NUS Medical School
                Award ID: GCR/2013/010
                Award ID: GCR/2013/011
                Categories
                Review Article

                Comments

                Comment on this article