49
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Glioma: experimental models and reality

      review-article

      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

          In theory, in vitro and in vivo models for human gliomas have great potential to not only enhance our understanding of glioma biology, but also to facilitate the development of novel treatment strategies for these tumors. For reliable prediction and validation of the effects of different therapeutic modalities, however, glioma models need to comply with specific and more strict demands than other models of cancer, and these demands are directly related to the combination of genetic aberrations and the specific brain micro-environment gliomas grow in. This review starts with a brief introduction on the pathological and molecular characteristics of gliomas, followed by an overview of the models that have been used in the last decades in glioma research. Next, we will discuss how these models may play a role in better understanding glioma development and especially in how they can aid in the design and optimization of novel therapies. The strengths and weaknesses of the different models will be discussed in light of genotypic, phenotypic and metabolic characteristics of human gliomas. The last part of this review provides some examples of how therapy experiments using glioma models can lead to deceptive results when such characteristics are not properly taken into account.

          Related collections

          Most cited references103

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

          Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system.

          Neurogenesis in the mammalian central nervous system is believed to end in the period just after birth; in the mouse striatum no new neurons are produced after the first few days after birth. In this study, cells isolated from the striatum of the adult mouse brain were induced to proliferate in vitro by epidermal growth factor. The proliferating cells initially expressed nestin, an intermediate filament found in neuroepithelial stem cells, and subsequently developed the morphology and antigenic properties of neurons and astrocytes. Newly generated cells with neuronal morphology were immunoreactive for gamma-aminobutyric acid and substance P, two neurotransmitters of the adult striatum in vivo. Thus, cells of the adult mouse striatum have the capacity to divide and differentiate into neurons and astrocytes.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Brain tumour cells interconnect to a functional and resistant network.

            Astrocytic brain tumours, including glioblastomas, are incurable neoplasms characterized by diffusely infiltrative growth. Here we show that many tumour cells in astrocytomas extend ultra-long membrane protrusions, and use these distinct tumour microtubes as routes for brain invasion, proliferation, and to interconnect over long distances. The resulting network allows multicellular communication through microtube-associated gap junctions. When damage to the network occurred, tumour microtubes were used for repair. Moreover, the microtube-connected astrocytoma cells, but not those remaining unconnected throughout tumour progression, were protected from cell death inflicted by radiotherapy. The neuronal growth-associated protein 43 was important for microtube formation and function, and drove microtube-dependent tumour cell invasion, proliferation, interconnection, and radioresistance. Oligodendroglial brain tumours were deficient in this mechanism. In summary, astrocytomas can develop functional multicellular network structures. Disconnection of astrocytoma cells by targeting their tumour microtubes emerges as a new principle to reduce the treatment resistance of this disease.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Optimized survival of hippocampal neurons in B27-supplemented Neurobasal, a new serum-free medium combination.

              We have systematically optimized the concentrations of 20 components of a previously published serum-free medium (Brewer and Cotman, Brain Res 494: 65-74, 1989) for survival of rat embryonic hippocampal neurons after 4 days in culture. This serum-free medium supplement, B27, produced neuron survival above 60%, independent of plating density above 160 plated cells/mm2. For isolated cells (< 100 cells/mm2), survival at 4 days was still above 45%, but could be rescued to the 60% level at 40 cells/mm2 by simply applying a coverslip on top of the cells. This suggests a need for additional trophic factors. High survival was achieved with osmolarity lower than found in Dulbecco's Modified Eagle's Medium (DMEM), and by reducing cysteine and glutamine concentrations and by the elimination of toxic ferrous sulphate found in DME/F12. Neurobasal is a new medium that incorporates these modifications to DMEM. In B27/Neurobasal, glial growth is reduced to less than 0.5% of the nearly pure neuronal population, as judged by immunocytochemistry for glial fibrillary acidic protein and neuron-specific enolase. Excellent long-term viability is achieved after 4 weeks in culture with greater than 90% viability for cells plated at 640/mm2 and greater than 50% viability for cells plated at 160/mm2. Since the medium also supports the growth of neurons from embryonic rat striatum, substantia nigra, septum, and cortex, and neonatal dentate gyrus and cerebellum (Brewer, in preparation), support for other neuron types is likely. B27/Neurobasal should be useful for in vitro studies of neuronal toxicology, pharmacology, electrophysiology, gene expression, development, and effects of growth factors and hormones.
                Bookmark

                Author and article information

                Contributors
                +31-243614289 , William.leenders@radboudumc.nl
                Journal
                Acta Neuropathol
                Acta Neuropathol
                Acta Neuropathologica
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0001-6322
                1432-0533
                10 January 2017
                10 January 2017
                2017
                : 133
                : 2
                : 263-282
                Affiliations
                [1 ]ISNI 0000 0004 0444 9382, GRID grid.10417.33, Department of Pathology, , Radboud University Medical Center, ; PO Box 9101, 6500 HB Nijmegen, The Netherlands
                [2 ]ISNI 0000 0004 0374 0039, GRID grid.249880.f, , The Jackson Laboratory for Genomic Medicine, ; Farmington, CT USA
                [3 ]ISNI 0000 0004 0444 9382, GRID grid.10417.33, Department of Neurosurgery, , Radboud University Medical Center, ; Nijmegen, The Netherlands
                [4 ]ISNI 0000 0004 0435 165X, GRID grid.16872.3a, Department of Pathology, , VU University Medical Center, ; Amsterdam, The Netherlands
                [5 ]ISNI 0000000090126352, GRID grid.7692.a, Department of Pathology, , Princess Máxima Center for Pediatric Oncology and University Medical Center Utrecht, ; Utrecht, The Netherlands
                Article
                1671
                10.1007/s00401-017-1671-4
                5250671
                28074274
                aa1977b5-8494-4a4b-a7d4-b7f01095c810
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 28 October 2016
                : 6 January 2017
                : 6 January 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004622, KWF Kankerbestrijding;
                Award ID: UvA2014-6839
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: NIH/NCI R01 CA190121
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100001512, National Brain Tumor Society;
                Categories
                Review
                Custom metadata
                © Springer-Verlag Berlin Heidelberg 2017

                Neurology
                Neurology

                Comments

                Comment on this article