Skip to main content
SpringerLink
Log in

Cancer Stem Cells in Brain Tumors

  • Chapter
  • First Online:
Stem Cells in Cancer: Should We Believe or Not?

  • 946 Accesses

Abstract

Some small-sized studies have suggested that CD133 expression and the ability for neurosphere formation have prognostic value in glioblastomas. In a large scale expression study, human glioblastomas were grouped in proliferative, proneural, and mesenchymal tumors. Neural stem cell markers, including CD133 and the formation of neurospheres were upregulated in molecular proliferative subtypes that correlate with a poor prognosis. Thus, CD133 expression and the formation of tumorspheres are completely absent in secondary glioblastomas, which are histologically similar, but different from a molecular point of view with respect to primary glioblastomas. Anaplastic oligodendrogliomas, oligoastrocytomas and glioblastomas with an oligodendroglial component are high grade oligodendroglial tumors, which are difficult to classify because of intratumoral diversity and the absence of clear cut histological markers. It is known that the frequency of tumor sphere growth and a CD133(+) population in high grade oligodendroglial tumors is related with a poor prognosis. Taken together, the presence of CD133(+) stem cells or cell populations with other stem cell biomarkers, and the frequency of tumor sphere formation may become a useful criterion for predicting the response to therapy and for establishing new prognosis glioma subtypes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Pardal R, Clarke M, Morrison S (2003) Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 3:895–902

    Article  PubMed  CAS  Google Scholar 

  2. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414(6859):105–111

    Article  PubMed  CAS  Google Scholar 

  3. Dick JE (2003) Breast cancer stem cells revealed. Proc Natl Acad Sci U S A 100(7):3547–3549

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63(18):5821–5828

    PubMed  CAS  Google Scholar 

  5. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432(7015):396–401

    Article  PubMed  CAS  Google Scholar 

  6. Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–1710

    Article  PubMed  CAS  Google Scholar 

  7. Vescovi AL, Reynolds BA, Fraser DD et al (1993) bFGF regulates the proliferative fate of unipotent (neuronal) and bipotent (neuronal/astroglial) EGF-generated CNS progenitor cells. Neuron 11:951–966

    Article  PubMed  CAS  Google Scholar 

  8. Reynolds BA, Weiss S (1996) Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic C N S precursor is a stem cell. Dev Biol 175:1–13

    Article  PubMed  CAS  Google Scholar 

  9. Galli R, Binda E, Orfanelli U et al (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64:7011–7021

    Article  PubMed  CAS  Google Scholar 

  10. Liu Y, Han SS, Wu Y et al (2004) CD44 expression identifies astrocyte-restricted precursor cells. Dev Biol 276:31–46

    Article  PubMed  CAS  Google Scholar 

  11. Rebetz J, Tian D, Persson A et al (2008) Glial progenitor-like phenotype in low-grade glioma and enhanced CD133-expression and neuronal lineage differentiation potential in high-grade glioma. PLoS One 3:e1936

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. Weiss WA, Burns MJ, Hackett C et al (2003) Genetic determinants of malignancy in a mouse model for oligodendroglioma. Cancer Res 63:1589–1595

    PubMed  CAS  Google Scholar 

  13. Corbeil D, Joester A, Fargeas CA et al (2009) Expression of distinct splice variants of the stem cell marker prominin-1 (CD133) in glial cells. Glia 57:860–874

    Article  PubMed  Google Scholar 

  14. Yang ZJ, Ellis T, Markant SL et al (2008) Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells. Cancer Cell 14:135–145

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  15. Read TA, Fogarty MP, Markant SL et al (2009) Identification of CD15 as a marker for tumor-propagating cells in a mouse model of medulloblastoma. Cancer Cell 15:135–147

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  16. Corti S, Nizzardo M, Nardini M et al (2007) Isolation and characterization of murine neural stem/progenitor cells based on Prominin-1 expression. Exp Neurol 205:547–562

    Article  PubMed  CAS  Google Scholar 

  17. 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 

  18. Vescovi AL, Galli R, Reynolds BA (2006) Brain tumour stem cells. Nat Rev Cancer 6:425–436

    Article  PubMed  CAS  Google Scholar 

  19. Sakariassen PO, Immervoll H, Chekenya M (2007) Cancer stem cells as mediators of treatment resistance in brain tumors: status and controversies. Neoplasia 9:882–892

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  20. Hamburger AW, Salmon SE (1977) Primary bioassay of human tumor stem cells. Science 197:461–463

    Article  PubMed  CAS  Google Scholar 

  21. Lee J, Kotliarova S, Kotliarov Y et al (2006) Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell 9:391–403

    Article  PubMed  CAS  Google Scholar 

  22. Sanai N, Alvarez-Buylla A, Berger MS (2005) Neural stem cells and the origin of gliomas. N Engl J Med 353:811–822

    Article  PubMed  CAS  Google Scholar 

  23. Bernier PJ, Vinet J, Cossette M, Parent A (2000) Characterization of the subventricular zone of the adult human brain: evidence for the involvement of Bcl-2. Neurosci Res 37(1):67–78

    Article  PubMed  CAS  Google Scholar 

  24. Chaichana KL, Capilla-Gonzalez V, Gonzalez-Perez O et al (2007) Preservation of glial cytoarchitecture from ex vivo human tumor and non-tumor cerebral cortical explants: a human model to study neurological diseases. J Neurosci Methods 164:261–270

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  25. Quinones-Hinojosa A, Sanai N, Soriano-Navarro M et al (2006) Cellular composition and cytoarchitecture of the adult human subventricular zone: a niche of neural stem cells. J Comp Neurol 494:415–434

    Article  PubMed  Google Scholar 

  26. Lim DA, Cha S, Mayo MC et al (2007) Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype. Neuro Oncol 9:424–429

    Article  PubMed Central  PubMed  Google Scholar 

  27. Gritti A, Parati EA, Cova L et al (1996) Multipotential stem cells from the adult mouse brain proliferate and self-renew in response to basic fibroblast growth factor. J Neurosci 16:1091–1100

    PubMed  CAS  Google Scholar 

  28. Menn B, Garcia-Verdugo JM, Yaschine C et al (2006) Origin of oligodendrocytes in the subventricular zone of the adult brain. J Neurosci 26:7907–7918

    Article  PubMed  CAS  Google Scholar 

  29. Jackson EL, Garcia-Verdugo JM, Gil-Perotin S et al (2006) PDGFR alpha-positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling. Neuron 51:187–199

    Article  PubMed  CAS  Google Scholar 

  30. Singh SK, Clarke ID, Hide T et al (2004) Cancer stem cells in nervous system tumors. Oncogene 23:7267–7273

    Article  PubMed  CAS  Google Scholar 

  31. Dirks PB (2005) Brain tumor stem cells. Biol Blood Marrow Transplant 11:12–13

    Article  PubMed  Google Scholar 

  32. Holland EC, Celestino J, Dai C et al (2000) Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nat Genet 25:55–57

    Article  PubMed  CAS  Google Scholar 

  33. Doetsch F, Caille I, Lim DA et al (1999) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97:703–716

    Article  PubMed  CAS  Google Scholar 

  34. Alcantara Llaguno S, Chen J, Kwon CH et al (2009) Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell 15:45–56

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  35. Dai C, Celestino JC, Okada Y et al (2001) PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo. Genes Dev 15:1913–1925

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  36. Persson A, Petritsch C, Itsara M et al (2010) Non-stem cell origin of oligodendondrogliomas. Cancer Cell 18:669–682

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  37. Ivkovic S, Canoll P, Goldman JE (2008) Constitutive EGFR signaling in oligodendrocyte progenitors leads to diffuse hyperplasia in postnatal white matter. J Neurosci 28:914–922

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  38. Ligon KL, Alberta JA, Kho AT et al (2004) The oligodendroglial lineage marker OLIG2 is universally expressed in diffuse gliomas. J Neuropathol Exp Neurol 63:499–509

    PubMed  CAS  Google Scholar 

  39. Beier D, Wischhusen J, Dietmaier W et al (2008) CD133 expression and cancer stem cells predict prognosis in high-grade oligodendroglial tumors. Brain Pathol 18:370–377

    Article  PubMed  Google Scholar 

  40. Harris MA, Yang H, Low BE et al (2008) Cancer stem cells are enriched in the side population cells in a mouse model of glioma. Cancer Res 68:10051–10059

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  41. Morrison SJ, Kimble J (2006) Asymmetric and symmetric stem-cell divisions in development and cancer. Nature 441:1068–1074

    Article  PubMed  CAS  Google Scholar 

  42. Fuller GN, Kros JM (2007) Gliomatosis cerebri. In: Louis DN, Ohgaki H, Wiestler OD et al (eds) WHO classification of tumours of the central nervous system, 4th edn. IARC, Lyon, pp 218–221

    Google Scholar 

  43. Balko MG, Blisard KS, Smamha J (1992) Oligodendroglial gliomatosis cerebri. Human Pathol 23:706–707

    Article  CAS  Google Scholar 

  44. Pal L, Behari S, Kumar S et al (2008) Gliomatosis cerebri – an uncommon neuroepithelial tumor in children with oligodendroglial phenotype. Pediatr Neurosurg 44:212–215

    Article  PubMed  Google Scholar 

  45. Bernsen H, Van der Laak J, Küsters B et al (2005) Gliomatosis cerebri: quantitative proof of vessel recruitment by cooptation instead of angiogenesis. J Neurosurg 103:702–706

    Article  PubMed  Google Scholar 

  46. Vates GE, Chang S, Lamborn KR et al (2003) Gliomatosis cerebri: a review of 22 cases. Neurosurgery 53:261–271

    Article  PubMed  Google Scholar 

  47. Romeike BF, Mawrin C (2009) MAP-2 immunoexpression in gliomatosis cerebri. Histopathology 54:504–505

    Article  PubMed  Google Scholar 

  48. Romeike BF, Mawrin C (2008) Gliomatosis cerebri: growing evidence for diffuse gliomas with wide invasion. Expert Rev Neurother 8:587–597

    Article  PubMed  Google Scholar 

  49. Kunishio K, Okada M, Matsumoto Y, Nagao S (2003) Matrix metalloproteinase-2 and -9 expression in astrocytic tumors. Brain Tumor Pathol 20:39–45

    Article  PubMed  CAS  Google Scholar 

  50. Mawrin C, Schneider T, Firsching R et al (2005) Assessment of tumor cell invasion factors in gliomatosis cerebri. J Neurooncol 73:109–115

    Article  PubMed  CAS  Google Scholar 

  51. Yamada SM, Hayashi Y, Takahashi H et al (2001) Histological and genetic diagnosis of gliomatosis cerebri: case report. J Neurooncol 52:237–240

    Article  PubMed  CAS  Google Scholar 

  52. Smith KM, Ohkubo Y, Maragnoli ME et al (2006) Midline radial glia translocation and corpus callosum formation require F G F signaling. Nat Neurosci 9:787–797

    Article  PubMed  CAS  Google Scholar 

  53. Ma DK, Ponnusamy K, Song MR et al (2009) Molecular genetic analysis of FGFR1 signalling reveals distinct roles of MAPK and PLCgamma1 activation for self-renewal of adult neural stem cells. Mol Brain 2:16–29

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  54. Hilbig A, Barbosa-Coutinho LM, Toscani N et al (2006) Expression of nestin and vimentin in gliomatosis cerebri. Arq Neuropsiquiatr 64:781–786

    Article  PubMed  Google Scholar 

  55. Kong DS, Kim MH, Park WY et al (2008) The progression of gliomas is associated with cancer stem cell phenotype. Oncol Rep 19:639–643

    PubMed  CAS  Google Scholar 

  56. Gunther 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  CAS  Google Scholar 

  57. Shen Q, Wang Y, Kokovay E et al (2008) Adult S V Z stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions. Cell Stem Cell 3:289–300

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  58. 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 

  59. Yang ZJ, Wechsler-Reya RJ (2007) Hit ‘em where they live: targeting the cancer stem cell niche. Cancer Cell 11:3–5

    Article  PubMed  CAS  Google Scholar 

  60. Quintana E, Shackleton M, Sabel MS et al (2008) Efficient tumour formation by single human melanoma cells. Nature 456:593–598

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  61. Doetsch 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  PubMed  CAS  Google Scholar 

  62. Capela A, Temple S (2002) LeX/ssea-1 is expressed by adult mouse CNS stem cells, identifying them as nonependymal. Neuron 35:865–875

    Article  PubMed  Google Scholar 

  63. Phillips HS, Kharbanda S, Chen R et al (2006) Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9:157–173

    Article  PubMed  CAS  Google Scholar 

  64. Kleihues P, Ohgaki H (1999) Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro Oncol 1:44–51

    PubMed Central  PubMed  CAS  Google Scholar 

  65. Bao S, Wu Q, McLendon RE et al (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–760

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Deparment of Medical Oncology, Servicio de Oncología Médica, Hospital Edgardo Rebagliati Martins, Lima, Peru

    Fernando Hurtado de Mendoza

  2. Unidad de Oncología de la Clínica San Felipe, Lima, Peru

    Fernando Hurtado de Mendoza

  3. Servicio de Oncología Médica, Hospital Edgardo Rebagliati Martins, Lima, Peru

    Enrique Alanya Rodriguez

  4. Centro de Oncologia Integral “ALIADA”, Lima, Peru

    Enrique Alanya Rodriguez

Authors
  1. Fernando Hurtado de Mendoza
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Enrique Alanya Rodriguez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fernando Hurtado de Mendoza .

Editor information

Editors and Affiliations

  1. Medical Oncology, Ramón y Cajal University Hospital, Madrid, Spain

    Enrique Grande

  2. Medical Oncology, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain

    Luis Antón Aparicio

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

de Mendoza, F.H., Rodriguez, E.A. (2014). Cancer Stem Cells in Brain Tumors. In: Grande, E., Antón Aparicio, L. (eds) Stem Cells in Cancer: Should We Believe or Not?. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8754-3_11

Download citation

Publish with us

Policies and ethics

Search

Navigation