title: Critical multiple angiogenic factors secreted by glioblastoma stem-like cells underline the need for combinatorial anti-angiogenic therapeutic strategies.
abstract: Glioblastomas are the most frequent adult primary brain tumors that still remain fatal despite major clinical efforts. As in other solid tumors, populations of glioblastoma stem-like cells (GSCs) endowed with tumor initiating and therapeutic resistance properties have been identified. Glioblastomas are highly vascularized tumors resulting in a rich dialog between GSCs and endothelial cells. In one direction, endothelial cells and their secreted proteins are able to sustain GSC properties while, in turn, GSCs can promote neoangiogenesis, modulate endothelial cell functions and may even transdifferentiate into endothelial cells. Accordingly, targeting tumor vasculature seems a promising issue despite incomplete and transient results obtained from anti-vascular endothelial growth factor therapeutic trials. Recent findings of novel GSC-secreted molecules with pro-angiogenic properties (Semaphorin 3A, hepatoma-derived growth factor) open the path to the design of a concerted attack of glioblastoma vasculature that could overcome the development of resistance to single-targeted therapies while keeping away the toxicity of the treatments.
authors.affiliation: Leukemia and Stem Cell Biology Laboratory, Department of Hematological Medicine, Rayne Institute, King's College London, London, UK.
authors.forename: Cécile
authors.initials: C
authors.lastname: Thirant
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: D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism*
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; C051610:hepatoma-derived growth factor