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Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors.

Authors
  • Q, Liu
  • Dh, Nguyen
  • Q, Dong
  • P, Shitaku
  • K, Chung
  • Oy, Liu
  • Jl, Tso
  • Jy, Liu
  • V, Konkankit
  • Tf, Cloughesy
  • Ps, Mischel
  • Tf, Lane
  • Lm, Liau
  • Stanley F. Nelson
  • Cl, Tso
Type
Published Article
Journal
Journal of Neuro-Oncology
Publisher
Springer-Verlag
Volume
94
Issue
1
Pages
1–19
Identifiers
DOI: 10.1007/s11060-009-9919-z
Source
Nelson Lab
License
Unknown

Abstract

Glioblastoma multiforme (GBM) remains refractory to conventional therapy. CD133+ GBM cells have been recently isolated and characterized as chemo-/radio-resistant tumor-initiating cells and are hypothesized to be responsible for post-treatment recurrence. In order to explore the molecular properties of tumorigenic CD133+ GBM cells that resist treatment, we isolated CD133+ GBM cells from tumors that are recurrent and have previously received chemo-/radio-therapy. We found that the purified CD133+ GBM cells sorted from the CD133+ GBM spheres express SOX2 and CD44 and are capable of clonal self-renewal and dividing to produce fast-growing CD133- progeny, which form the major cell population within GBM spheres. Intracranial injection of purified CD133+, not CD133- GBM daughter cells, can lead to the development of YKL-40+ infiltrating tumors that display hypervascularity and pseudopalisading necrosis-like features in mouse brain. The molecular profile of purified CD133+ GBM cells revealed characteristics of neuroectoderm-like cells, expressing both radial glial and neural crest cell developmental genes, and portraying a slow-growing, non-differentiated, polarized/migratory, astrogliogenic, and chondrogenic phenotype. These data suggest that at least a subset of treated and recurrent GBM tumors may be seeded by CD133+ GBM cells with neural and mesenchymal properties. The data also imply that CD133+ GBM cells may be clinically indolent/quiescent prior to undergoing proliferative cell division (PCD) to produce CD133- GBM effector progeny. Identifying intrinsic and extrinsic cues, which promote CD133+ GBM cell self-renewal and PCD to support ongoing tumor regeneration may highlight novel therapeutic strategies to greatly diminish the recurrence rate of GBM.

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