Differential proteomic analysis of human glioblastoma and neural stem cells reveals HDGF as a novel angiogenic secreted factor

Stem Cells. 2012 May;30(5):845-53. doi: 10.1002/stem.1062.


Presence in glioblastomas of cancer cells with normal neural stem cell (NSC) properties, tumor initiating capacity, and resistance to current therapies suggests that glioblastoma stem-like cells (GSCs) play central roles in glioblastoma development. We cultured human GSCs endowed with all features of tumor stem cells, including tumor initiation after xenograft and radio-chemoresistance. We established proteomes from four GSC cultures and their corresponding whole tumor tissues (TTs) and from human NSCs. Two-dimensional difference gel electrophoresis and tandem mass spectrometry revealed a twofold increase of hepatoma-derived growth factor (HDGF) in GSCs as compared to TTs and NSCs. Western blot analysis confirmed HDGF overexpression in GSCs as well as its presence in GSC-conditioned medium, while, in contrast, no HDGF was detected in NSC secretome. At the functional level, GSC-conditioned medium induced migration of human cerebral endothelial cells that can be blocked by anti-HDGF antibodies. In vivo, GSC-conditioned medium induced neoangiogenesis, whereas HDGF-targeting siRNAs abrogated this effect. Altogether, our results identify a novel candidate, by which GSCs can support neoangiogenesis, a high-grade glioma hallmark. Our strategy illustrates the usefulness of comparative proteomic analysis to decipher molecular pathways, which underlie GSC properties.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiogenesis Inducing Agents / metabolism*
  • Animals
  • Cell Movement
  • Culture Media, Conditioned
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Female
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Mice
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / pathology
  • Neural Stem Cells / metabolism*
  • Neural Stem Cells / pathology
  • Proteomics*
  • Transplantation, Heterologous
  • Tumor Cells, Cultured


  • Angiogenesis Inducing Agents
  • Culture Media, Conditioned
  • Intercellular Signaling Peptides and Proteins
  • hepatoma-derived growth factor