title: Differential proteomic analysis of human glioblastoma and neural stem cells reveals HDGF as a novel angiogenic secreted factor.
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.
authors.affiliation: INSERM U894, Psychiatry and Neuroscience Center, Glial Plasticity Team, Cochin Institute, Paris Descartes University, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Thirant
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Galan-Moya
authors.forename: Luiz Gustavo
authors.initials: LG
authors.lastname: Dubois
authors.forename: Sébastien
authors.initials: S
authors.lastname: Pinte
authors.forename: Philippe
authors.initials: P
authors.lastname: Chafey
authors.forename: Cédric
authors.initials: C
authors.lastname: Broussard
authors.forename: Pascale
authors.initials: P
authors.lastname: Varlet
authors.forename: Bertrand
authors.initials: B
authors.lastname: Devaux
authors.forename: Fabrice
authors.initials: F
authors.lastname: Soncin
authors.forename: Julie
authors.initials: J
authors.lastname: Gavard
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Junier
authors.forename: Hervé
authors.initials: H
authors.lastname: Chneiweiss
mesh_terms: D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement; D017077:Culture Media, Conditioned; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology; D040901:Proteomics; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D043925:Angiogenesis Inducing Agents; D017077:Culture Media, Conditioned; D036341:Intercellular Signaling Peptides and Proteins; C051610:hepatoma-derived growth factor