Cell Prolif.
2005,38, 423–433
Cancer stem cells in CNS
G. J. Pilkington
REVIEW
Cancer stem cells in the mammalian central nervous system
G. J. Pilkington
Cellular and Molecular Neuro-oncology Research Group, Institute of Biomedical and Biomolecular Sciences,
School of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael’s Building, White Swan Road,
Portsmouth PO1 2DT, UK
Received 8 July 2005; revision accepted
2 September 2005
Abstract.
Malignant tumours intrinsic to the central nervous system (CNS) are
among the most difficult of neoplasms to treat effectively. The major biological features
of these tumours that preclude successful therapy include their cellular heterogeneity,
which renders them highly resistant to both chemotherapy and radiotherapy, and the
propensity of the component tumour cells to invade, diffusely, the contiguous nervous
tissues. The tumours are classified according to perceived cell of origin, gliomas being
the most common generic group. In the 1970s transplacental administration of the
potent neurocarcinogen, N-ethyl-N-nitrosourea (ENU), enabled investigation of the
sequential development of brain and spinal neoplasms by electron microscopy and
immunohistochemistry. The significance of the primitive cells of the subependymal
plate in cellular origin and evolution of a variety of glial tumours was thereby established.
Since then, the development of new cell culture methods, including the
in vitro
growth of neurospheres and multicellular tumour spheroids, and new antigenic markers
of stem cells and glial/neuronal cell precursor cells, including nestin, Mushashi-1 and
CD133, have led to a reappraisal of the histological classification and origins of CNS
tumours. Moreover, neural stem cells may also provide new vectors in exciting novel
therapeutic strategies for these tumours. In addition to the gliomas, stem cells may
have been identified in paediatric tumours including cerebellar medulloblastoma, thought
to be of external granule cell neuronal derivation. Interestingly, while the stem cell
marker CD133 is expressed in these primitive neuroectodermal tumours (PNETs), the
chondroitin sulphate proteoglycan neuronal/glial 2 (NG2), which appears to denote increased
proliferative, but reduced migratory activity in adult gliomas, is rarely expressed. This
is in contrast to the situation in the histologically similar supratentorial PNETs. A possible
functional ‘switch’ between proliferation and migration in developing neural tumour cells
may exist between NG2 and ganglioside GD3. The divergent pathways of differentiation
of CNS tumours and the possibility of stem cell origin, for some, if not all, such neoplasms
remain a matter for debate and continued research, but the presence of self-renewing
Correspondence: Professor Geoffrey J. Pilkington, Cellular and Molecular Neuro-oncology Research Group, Institute
of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth,
St Michael’s Building, White Swan Road, Portsmouth PO1 2DT, UK. Tel./Fax: +44 (0)23 92842116; E-mail:
geoff.pilkington@port.ac.uk
© 2005 Blackwell Publishing Ltd,
Cell Proliferation,38, 423–433.424
G. J. Pilkington
neural stem cells in the CNS of both children and adults strongly suggests a role for
these cells in tumour initiation and resistance to current therapeutic strategies.
