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

Qinghai Liu, David H. Nguyen, Qinghua Dong, Peter Shitaku, Kenneth Chung, On Ying Liu, Jonathan L. Tso, Jason Y. Liu, Veerauo Konkankit, Timothy F. Cloughesy, Paul S. Mischel, Timothy F Lane, Linda M. Liau, Stanley F. Nelson, Cho Lea Tso

Research output: Contribution to journalArticle

94 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-19
Number of pages19
JournalJournal of Neuro-Oncology
Volume94
Issue number1
DOIs
StatePublished - Jun 3 2009

    Fingerprint

Keywords

  • Cancer stem cells
  • Expression microarray
  • Glioblastoma
  • Neural crest cells
  • Radial glial cells
  • Self-renewal

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Liu, Q., Nguyen, D. H., Dong, Q., Shitaku, P., Chung, K., Liu, O. Y., Tso, J. L., Liu, J. Y., Konkankit, V., Cloughesy, T. F., Mischel, P. S., Lane, T. F., Liau, L. M., Nelson, S. F., & Tso, C. L. (2009). Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors. Journal of Neuro-Oncology, 94(1), 1-19. https://doi.org/10.1007/s11060-009-9919-z