Autocrine factors sustain glioblastoma stem cell self-renewal

Oncol Rep. 2009 Feb;21(2):419-24.

Abstract

Glioblastoma stem cells are able to reform original glioblastoma and express the neural stem cell marker CD133 and Nestin. They can self-renew and proliferate in tumor sphere medium containing EGF, bFGF and LIF that is known to be permissive for stem cell proliferation. In this study, we found that neurosphere-like colonies appeared after the human primary glioblastoma cells had been switched into pure DMEM/F12 medium. We investigated whether tumor spheres formed in pure DMEM/F12 medium possess the characteristics of glioblastoma stem cells. We identified that the tumor sphere cells were cancer stem cells of glioblastoma and they can self-renew and proliferate in pure DMEM/F12 medium. Glioblastoma cells can secrete several factors that result in autocrine motility signaling and stimulate glioma invasion. We hypothesized that an essential autocrine signal promotes the self-renewal and proliferation of human glioblastoma stem cells in pure DMEM/F12 medium. Then, expression of EGF and bFGF in glioblastoma stem cells were analyzed. Both the mRNA and protein of EGF and bFGF were detected in three human glioblastoma stem cells. Our findings suggest that autocrine of EGF and bFGF may sustain the self-renewal of glioblastoma stem cells.

MeSH terms

  • Animals
  • Autocrine Communication / physiology*
  • Blotting, Western
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Culture Media
  • Epidermal Growth Factor / metabolism
  • Fibroblast Growth Factor 2 / metabolism
  • Flow Cytometry
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Nude
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / pathology

Substances

  • Culture Media
  • Fibroblast Growth Factor 2
  • Epidermal Growth Factor