Elsevier

The Lancet Oncology

Volume 5, Issue 8, August 2004, Pages 511-514
The Lancet Oncology

Essay
Development of gliomas: potential role of asymmetrical cell division of neural stem cells

https://doi.org/10.1016/S1470-2045(04)01531-1Get rights and content

Summary

Asymmetrical cell division is a mechanism that gives rise to two daughter cells with different proliferative and differentiative fates. It occurs mainly during development and in adult stem cells. Accumulating evidence suggests that tumour cells arise from the transformation of normal stem cells. Here, we propose that the asymmetrical mitosis potential of stem cells is associated with the generation of migrating tumour progenitors. Application of this speculative model to glioma proposes that the sites where tumour-initiating stem cells reside are indolent and distinct from the tumour mass, and implies that the tumour mass is continuously replenished with new migrating tumour cells from these clinically silent regions. This hypothesis offers explanations for our inability to cure glioblastoma and points to asymmetrical division as a new potential therapeutic target.

Section snippets

Symmetrical versus asymmetrical division of stem cells

Cells can divide either symmetrically or asymmetrically.23, 24 Unlike conventional symmetrical mitosis that generates two identical daughter cells, asymmetrical cell division leads to the asymmetrical segregation of cell-fate determinants.23, 24, 25, 26, 27 Therefore, this mode of cell division generates two daughter cells with different cell fates (figure 1A).23, 24, 25, 26, 27 For example, the asymmetrical division of a stem cell gives rise to a selfrenewing stem cell and to a daughter cell,

Conclusion

Asymmetrical mitosis is an attribute of stem cells and progenitor cells which, if also present in cancer stem cells, could have important implications in cancer research. In gliomas, one consequence of our hypothetical model is that the asymmetrical division of cancer neural stem cells and the migration of cancer progenitors lead to separate locations for the tumour-initiating cell and the actual tumour mass. Moreover, because cancer neural stem cells that divide asymmetrically have a constant

Search strategy and selection criteria

Data for this essay were identified by searches of PubMed. The search terms were “asymmetric(al) division”, “stem cell”, “neural stem cell”, “cancer”, “glioma”. Other reports were identified from the personal collections of the authors. References from selected articles were also considered. Only articles published in English were considered.

References (48)

  • BredelM et al.

    Brain-tumour drug resistance: the bare essentials

    Lancet Oncol

    (2002)
  • LiL et al.

    PTEN in neuronal precursor cells: regulation of migration, apoptosis, and proliferation

    Mol Cell Neurosci

    (2002)
  • LewisPD

    Mitotic activity in the primate subependymal layer and the genesis of gliomas

    Nature

    (1968)
  • VickNA et al.

    The role of the subependymal plate in glial tumorigenesis

    Acta Neuropathol

    (1977)
  • LantosPL et al.

    The origin of experimental brain tumors: a sequential study

    Experientia

    (1976)
  • TaupinP et al.

    Adult neurogenesis and neural stem cells of the central nervous system in mammals

    J Neurosci

    (2002)
  • SmythGE et al.

    Tumors of the thalamus: a clinico-pathological study

    Brain

    (1938)
  • GlobusJH et al.

    Tumors of the striatothalamic and related regions: their probable source of origin and more common forms

    Arch Pathol

    (1942)
  • GlobusJH et al.

    The subependymal plate (matrix) and its relationship to brain tumors of the ependymal type

    J Neuropath Exp Neurol

    (1944)
  • BonnetD et al.

    Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell

    Nat Med

    (1997)
  • ReyaT et al.

    Stem cells, cancer, and cancer stem cells

    Nature

    (2001)
  • PasseguéE et al.

    Normal and leukemic hematopoiesis: are leukemias a stem cell disorder or a reacquisition of stem cell characteristics?

    Proc Natl Acad Sci USA

    (2003)
  • Perez-LosadaJ et al.

    Stem-cell hierarchy in skin cancer

    Nat Rev Cancer

    (2003)
  • KordonEC et al.

    An entire functional mammary gland may comprise the progeny from a single cell

    Development

    (1998)
  • Cited by (66)

    • Subventricular Zone Involvement Characterized by Diffusion Tensor Imaging in Glioblastoma

      2017, World Neurosurgery
      Citation Excerpt :

      This theory indicates that the tumor does not originate from the SVZ but rather grows toward it.19 Only half of GBMs may be initiated by cancer stem cells, whereas the other half arise from dedifferentiated mature glial cells, based on the anatomic location of the tumor according to Lim et al.20 Contrary to this theory, Berger et al.21 proposed that cells can, besides normal mitosis, undergo an asymmetric division. In stem cells, this theory means that the mother stem cell divides into 1 self-renewing stem cell and 1 progenitor cell, which can further differentiate.

    View all citing articles on Scopus
    View full text