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A Theory and a Model to Understand Glioblastoma Development Both in the Bulk and in the Microinfiltrated Brain Parenchyma

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Abstract

The prognosis of patients affected by glioblastoma remains dismal despite many efforts have been devoted worldwide in research and therapeutic strategies. Reasons of our failure include the fact that the patient harboring a glioblastoma always has two problems inside the brain, the bulk tumor and the parenchyma microinfiltrated; the other reason is that the tumor is able to grow dynamically adapting to the mutated conditions of its growth microenvironment. This paper tries to give an interpretation to the dynamic process of the tumor growth, from the beginning to the end of its natural history, dividing it in three phases, one pre-hypoxia and two post-hypoxia, and these are then correlated with the types of cancer stem cells (CSCs) involved. Furthermore, the paper proposes an original animal model to follow glioblastoma development in only one generation of mice, both in the bulk and in the brain parenchyma.

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References

  1. Mikkelsen T, Bjerkvig R, Lærum OD et al (1998) Brain tumor invasion. Wiley-Liss, New York

    Google Scholar 

  2. Shen Q, Wang Y, Kokavay E et al (2008) Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell–cell interactions. Cell Stem Cell 3:289–300

    Article  PubMed  CAS  Google Scholar 

  3. Hall PE, Lathia JD, Miller NGA et al (2006) Integrins are markers of human neural stem cells. Stem Cells 24:2078–2084

    Article  PubMed  CAS  Google Scholar 

  4. Singh SK, Clarke ID, Terasaki M et al (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821–5828

    PubMed  CAS  Google Scholar 

  5. Singh SK, Hawkins C, Clarke ID et al (2004) Identification of human brain tumour initiating cells. Nature 432:396–401

    Article  PubMed  CAS  Google Scholar 

  6. Beier D, Hau P, Proescholdt M et al (2007) CD133+ and CD133− glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res 67:4010–4015

    Article  PubMed  CAS  Google Scholar 

  7. Günther HS, Schmidt NO, Phillips HS et al (2008) Glioblastoma-derived stem cell-enriched cultures form distinct subgroups according to molecular and phenotypic criteria. Oncogene 27:2897–2909

    Article  PubMed  Google Scholar 

  8. Lottaz C, Beier D, Meyer K et al (2010) Transcriptional profiles of CD133+ and CD133− glioblastoma-derived cancer stem cell lines suggest different cells of origin. Cancer Res 70:2030–2040

    Article  PubMed  CAS  Google Scholar 

  9. Pfenninger CV, Roschupkina T, Hertwig F et al (2007) CD133 is not present on neurogenic astrocytes in the adult subventricular zone, but on embryonic neural stem cells, ependymal cells, and glioblastoma cells. Cancer Res 67:5727–5736

    Article  PubMed  CAS  Google Scholar 

  10. Coskun V, Wu H, Blanchi B et al (2008) CD133+ neural stem cells in the ependyma of mammalian postnatal forebrain. Proc Natl Acad Sci USA 105(3):1026–1031

    Article  PubMed  CAS  Google Scholar 

  11. Taylor MD, Poppleton H, Fuller C et al (2005) Radial glia cells are candidate stem cells of ependymoma. Cancer Cell 8:323–335

    Article  PubMed  CAS  Google Scholar 

  12. Doetch F, Petreanu L, Caille I et al (2002) EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells. Neuron 36:1021–1034

    Article  Google Scholar 

  13. Evans SM, Judy KD, Dunphy I et al (2004) Hypoxia is important in the biology and aggression of human glial brain tumors. Clin Cancer Res 10:8177–8184

    Article  PubMed  CAS  Google Scholar 

  14. McCord AM, Jamal M, Shankavarum UT et al (2009) Physiologic oxygen concentration enhances the stem-like properties of CD133+ human glioblastoma cells in vitro. Mol Cancer Res 7:489–497

    Article  PubMed  CAS  Google Scholar 

  15. Dings J, Meixensberger J, Jager A et al (1998) Clinical experience with 118 brain tissue oxygen partial pressure catheter probes. Neurosurgery 43:1082–1095

    Article  PubMed  CAS  Google Scholar 

  16. Evans SM, Judy KD, Dunphy I et al (2004) Comparative measurements of hypoxia in human brain tumors using needle electrodes and EF5 binding. Cancer Res 64:1886–1892

    Article  PubMed  CAS  Google Scholar 

  17. Vaupel P (2004) The role of hypoxia-induced factors in tumor progression. The Oncologist 9(suppl 5):10–17

    Article  PubMed  CAS  Google Scholar 

  18. Vaupel P (2008) Hypoxia and aggressive tumor phenotype: implications for therapy and prognosis. The Oncologist 13(suppl 3):21–26

    Article  PubMed  CAS  Google Scholar 

  19. Griguer CE, Oliva CR, Gobin E et al (2008) CD133 is a marker of bioenergetic stress in human glioma. PLoS ONE 3(11):e3655

    Article  PubMed  Google Scholar 

  20. Blazek ER, Foutch JL, Maki G (2007) Daoy medulloblastoma cells that express CD133 are radioresistant relative to CD133-cells, and the CD133+ sector is enlarged by hypoxia. Int J Radiat Oncol Biol Phys 67:1–5

    Article  PubMed  CAS  Google Scholar 

  21. Platet N, Liu SY, Atifi ME et al (2007) Influence of oxygen tension on CD133 phenotype in human glioma cell cultures. Cancer Lett 258:286–290

    Article  PubMed  CAS  Google Scholar 

  22. Warburg O (1956) On the origin of cancer cells. Science 123:309–314

    Article  PubMed  CAS  Google Scholar 

  23. Warburg O (1956) On respiratory impairment in cancer cells. Science 124:269–270

    PubMed  CAS  Google Scholar 

  24. Griguer CE, Oliva C, Gillepsie GY (2005) Glucose metabolism heterogeneity in human and mouse malignant glioma cell lines. J Neurooncol 74:123–133

    Article  PubMed  CAS  Google Scholar 

  25. Kallinowski F, Schlenger KH, Kloes M et al (1989) Tumor blood flow: the principal modulator of oxidative and glycolytic metabolism, and of the metabolic micromilieu of human tumor xenografts in vivo. Int J Cancer 44:266–272

    Article  PubMed  CAS  Google Scholar 

  26. Kania G, Corbeil D, Fuchs J et al (2005) Somatic stem cell marker prominin1/CD133 is expressed in embryonic stem cell-derived progenitors. Stem Cells 23:791–804

    Article  PubMed  CAS  Google Scholar 

  27. Beckner ME, Gobbel GT, Abounader R et al (2005) Glycolytic glioma cells with active glycogen synthase are sensitive to PTEN and inhibitors of PI3K and gluconeogenesis. Lab Invest 85:1457–1470

    Article  PubMed  CAS  Google Scholar 

  28. Bouzier AK, Voisin P, Goodwin R et al (1998) Glucose and lactate metabolism in C6 glioma cells: evidence for the preferential utilization of lactate for cell oxydative metabolism. Dev Neurosci 20:331–338

    Article  PubMed  CAS  Google Scholar 

  29. Turcotte ML, Parliament M, Franko A et al (2002) Variation in mitochondrial function in hypoxia-sensitive and hypoxia-tolerant human glioma cells. Br J Cancer 86:619–624

    Article  PubMed  CAS  Google Scholar 

  30. Bao S, Wu Q, Li Z et al (2008) Targeting cancer stem cells through L1CAM suppresses glioma growth. Cancer Res 68:6043–6048

    Article  PubMed  CAS  Google Scholar 

  31. Ezashi T, Das P, Roberts MR (2005) Low O2 tensions and the prevention of differentiation of hES cells. Proc Natl Acad Sci USA 102:4783–4788

    Article  PubMed  CAS  Google Scholar 

  32. Li Z, Bao S, Wu Q et al (2009) Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell 15:501–513

    Article  PubMed  CAS  Google Scholar 

  33. Seidel S, Garvalov BK, Wirta V et al (2010) A hypoxic niche regulates glioblastoma stem cells through hypoxia inducible factor 2α. Brain 133:983–995

    Article  PubMed  Google Scholar 

  34. Zheng X, Sheng G, Yang X et al (2007) Most C6 cells are cancer stem cells: evidence from clonal and population analyses. Cancer Res 67:3691–3697

    Article  PubMed  CAS  Google Scholar 

  35. Keith B, Simon MC (2007) Hypoxia-inducible factors, stem cells, and cancer. Cell 129:465–472

    Article  PubMed  CAS  Google Scholar 

  36. Calabrese C, Poppleton H, Kocak M et al (2007) A perivascular niche for brain tumor stem cells. Cancer Cell 11:69–82

    Article  PubMed  CAS  Google Scholar 

  37. Castillejo CR, Sanchez–Sanchez F, Andreu-Agullo C et al (2006) Pigment epithelium-derived factor is a niche signal for neural stem cell renewal. Nat Neurosci 9:331–339

    Article  Google Scholar 

  38. Tavazoie M, Van der Veken L, Silva-Vargas V et al (2008) A specialized vascular niche for adult neural stem cells. Cell Stem Cell 3:279–288

    Article  PubMed  CAS  Google Scholar 

  39. Gingras MC, Roussel E, Bruner GM et al (1995) Comparison of cell adhesion molecule expression between glioblastoma multiforme and autologous normal brain tissue. J Neuroimmunol 57:143–153

    Article  PubMed  CAS  Google Scholar 

  40. Bellail AC, Hunter SB, Brat DJ et al (2004) Microregional extracellular matrix heterogeneity in brain modulates glioma cell invasion. The Intern Journ of Bioch Cell Biol 36:1046–1069

    Article  CAS  Google Scholar 

  41. Paul Mould A, Askari JA, Craig SE et al (1994) Integrin α4β1-mediated melanoma cell adhesion and migration on vascular cell adhesion molecule-1 (VCAM-1) and the alternatively spliced IIICS region of fibronectin. The Journ of Biol Chem 269:27224–27230

    Google Scholar 

  42. Sakariassen PØ, Prestegarden L, Wang J et al (2006) Angiogenesis-independent tumor growth mediated by stem-like cancer cells. Proc Natl Acad Sci USA 103:16466–16471

    Article  PubMed  CAS  Google Scholar 

  43. Park DM, Rich JN (2009) Biology of glioma cancer stem cells. Mol and cells 28:7–12

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosurgery, S. Maria della Misericordia Hospital, Rovigo, Italy

    Enrico Brognaro

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  1. Enrico Brognaro
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Correspondence to Enrico Brognaro.

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Brognaro, E. A Theory and a Model to Understand Glioblastoma Development Both in the Bulk and in the Microinfiltrated Brain Parenchyma. Neurochem Res 36, 2145–2154 (2011). https://doi.org/10.1007/s11064-011-0539-6

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  • DOI: https://doi.org/10.1007/s11064-011-0539-6

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