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Brain tumour stem cells

Key Points

  • Adult somatic stem cells are a rare population of long-lived cells that have significant proliferative capacity, show extensive self-renewal and have a wide differentiation potential.

  • Cells that have the cardinal properties of stem cells have been identified in restricted regions of the CNS, where they are arranged in specific lineage hierarchies.

  • Similar to other adult stem cells, neural stem cells or their immediate progeny, which are called transiently dividing progenitors, can be considered a credible target for malignant transformation. This concept is supported by the finding that many of the molecular determinants that regulate normal neurogenesis seem also to be involved in tumorigenesis.

  • Brain tumour stem cells have been identified and isolated from different types of brain tumour: in particular, glioblastoma multiforme and medulloblastoma.

  • Brain tumour stem cells show all the features of stem cells, including the ability to generate new tumours that faithfully reproduce the phenotype of the human disease.

  • The availability of brain tumour stem-cell lines provides a model system for the identification of specific antigenic and molecular markers that might target the tumour-initiating cell.

  • The development of agents that selectively target and inhibit the tumour-initiating and propagation potential of brain tumour stem cells might reduce or eliminate primary tumour establishment, growth and recurrence.


The dogma that the genesis of new cells is a negligible event in the adult mammalian brain has long influenced our perception and understanding of the origin and development of CNS tumours. The discovery that new neurons and glia are produced throughout life from neural stem cells provides new possibilities for the candidate cells of origin of CNS neoplasias. The emerging hypothesis is that alterations in the cellular and genetic mechanisms that control adult neurogenesis might contribute to brain tumorigenesis, thereby allowing the identification of new therapeutic strategies.

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Figure 1: The anatomy and functioning of the subventricular zone and subgranular zone in rodents and humans.
Figure 2: Hierarchical organization of the functional compartments in renewing tissues.
Figure 3: Isolation and perpetuation of brain tumour stem cells in culture.
Figure 4: Neurogenetic compartments as developmental 'beltways'.


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We are grateful to S. Piccirillo for valuable help with the preparation of this manuscript and to R. Rietze and M. De Palma for their useful suggestions and comments.

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Correspondence to Angelo L. Vescovi.

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Competing interests

A.L.V. is the director of research and owns shares in StemGen, a biotechnology company that is based in Milan, Italy.

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Abnormal ionic flux

Alterations in the transit of ions through specific channels (NMDA receptors) that is generated by the massive release of glutamate from damaged cells and which leads to excito-toxicity.


CNS injury that is produced by tumour-induced transient ischaemia followed by blood re-oxygenation, which induces neural damage through the generation of reactive oxygen species.

Resting embryonic-like tissue

Remnants of cells that maintain the features of embryonic cells but are located in a semi-quiescent mature tissue.

Nestin-expressing cells

Undifferentiated neural precursors that express the neuroepithelial intermediate filament nestin.

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Vescovi, A., Galli, R. & Reynolds, B. Brain tumour stem cells. Nat Rev Cancer 6, 425–436 (2006).

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