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- Title
Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors.
- Authors
Qinghai Liu; Nguyen, David; Qinghua Dong; Shitaku, Peter; Chung, Kenneth; On Liu; Tso, Jonathan; Liu, Jason; Konkankit, Veerauo; Cloughesy, Timothy; Mischel, Paul; Lane, Timothy; Liau, Linda; Nelson, Stanley; Cho-Lea Tso
- 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.
- Publication
Journal of Neuro-Oncology, 2009, Vol 94, Issue 1, p1
- ISSN
0167-594X
- Publication type
Academic Journal
- DOI
10.1007/s11060-009-9919-z