-
Views
-
Cite
Cite
Cécile Thirant, Eva‐Maria Galan‐Moya, Luiz Gustavo Dubois, Sébastien Pinte, Philippe Chafey, Cédric Broussard, Pascale Varlet, Bertrand Devaux, Fabrice Soncin, Julie Gavard, Marie‐Pierre Junier, Hervé Chneiweiss, Differential Proteomic Analysis of Human Glioblastoma and Neural Stem Cells Reveals HDGF as a Novel Angiogenic Secreted Factor, Stem Cells, Volume 30, Issue 5, May 2012, Pages 845–853, https://doi.org/10.1002/stem.1062
- Share Icon Share
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.
Disclosure of potential conflicts of interest is found at the end of this article.