Differential Proteomic Analysis of Human Glioblastoma and Neural Stem Cells Reveals HDGF as a Novel Angiogenic Secreted Factor

Citations Over TimeTop 10% of 2012 papers

Abstract

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.

Related Papers

• → Using the Neurosphere Assay to Quantify Neural Stem Cells In Vivo(2007)69 cited
• → The Neurosphere Assay Applied to Neural Stem Cells and Cancer Stem Cells(2013)21 cited
• → The Neurosphere Assay (NSA) Applied to Neural Stem Cells (NSCs) and Cancer Stem Cells (CSCs)(2019)9 cited
• Adenosine Promotes Proliferation of Neural Stem Cells in vitro(2008)
• Topiramate Promotes Proliferation of Neural Stem Cells in Vitro(2008)