Proliferation of human glioblastoma stem cells occurs independently of exogenous mitogens

John J.P. Kelly, Owen Stechishin, Andrew Chojnacki, Xueqing Lun, Beichen Sun, Donna L. Senger, Peter Forsyth, Roland N. Auer, Jeff F. Dunn, J. Gregory Cairncross, Ian F. Parney, Samuel Weiss

Research output: Contribution to journalArticlepeer-review

146 Scopus citations


Primary glial tumors of the central nervous system, most commonly glioblastoma multiforme (GBM), are aggressive lesions with a dismal prognosis. Despite identification and isolation of human brain tumor stem cells (BTSCs), characteristics that distinguish BTSCs from neural stem cells remain to be elucidated. We cultured cells isolated from gliomas, using the neurosphere culture system, to understand their growth requirements. Both CD133+ and CD133- adult GBM BTSCs proliferated in the absence of exogenous mitogenic stimulation and gave rise to multipotent GBM spheres that were capable of self-renewal. Epidermal growth factor (EGF) and fibroblast growth factor-2 enhanced GBM BTSC survival, proliferation, and subsequent sphere size. Blockade of EGF receptor (EGFR) signaling reduced exogenous mitogen-independent GBM sphere growth. Implantation of as few as 10 exogenous mitogen-independent GBM BTSCs led to the formation of highly invasive intracranial tumors, which closely resembled human GBMs, in immunocompromised mice. These results demonstrate that exogenous mitogen independence, mediated in part through EGFR signaling, is one characteristic that distinguishes CD133- and CD133- GBM BTSCs from neural stem cells. This novel experimental system will permit the elucidation of additional constitutively activated mechanisms that promote GBM BTSC survival, self-renewal, and proliferation.

Original languageEnglish (US)
Pages (from-to)1722-1733
Number of pages12
JournalStem Cells
Issue number8
StatePublished - Aug 2009


  • Brain tumor stem cell
  • Glioblastoma
  • Glioma
  • Mitogen
  • Neural stem cell

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology


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