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

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.

journal_name

J Neurooncol

journal_title

Journal of neuro-oncology

authors

Liu Q,Nguyen DH,Dong Q,Shitaku P,Chung K,Liu OY,Tso JL,Liu JY,Konkankit V,Cloughesy TF,Mischel PS,Lane TF,Liau LM,Nelson SF,Tso CL

doi

10.1007/s11060-009-9919-z

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

1-19

issue

eissn

0167-594X

issn

1573-7373

journal_volume

pub_type

杂志文章

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