title: Angiogenesis in gliomas: biology and molecular pathophysiology.
abstract: Glioblastoma multiforme (GBM) is characterized by exuberant angiogenesis, a key event in tumor growth and progression. The pathologic mechanisms driving this change and the biological behavior of gliomas remain unclear. One mechanism may involve cooption of native blood vessels by glioma cells inducing expression of angiopoietin-2 by endothelial cells. Subsequently, vascular apoptosis and involution leads to necrosis and hypoxia. This in turn induces angiogenesis that is associated with expression of hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor (VEGF) in perinecrotic pseudopalisading glioma cells. Here we review the molecular and cellular mechanisms implicated in HIF-1-dependent and HIF-1-independent glioma-associated angiogenesis. In GBMs, both tumor hypoxia and genetic alterations commonly occur and act together to induce the expression of HIF-1. The angiogenic response of the tumor to HIF-1 is mediated by HIF-1-regulated target genes leading to the upregulation of several proangiogenic factors such as VEGF and other adaptive response molecules. Understanding the roles of these regulatory processes in tumor neovascularization, tumor growth and progression, and resistance to therapy will ultimately lead to the development of improved antiangiogenic therapies for GBMs.
authors.affiliation: Microvascular and Molecular Neuro-oncology Laboratory, New York University School of Medicine, USA.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Fischer
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gagner
authors.forename: Meng
authors.initials: M
authors.lastname: Law
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Newcomb
authors.forename: David
authors.initials: D
authors.lastname: Zagzag
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply* / Q000473:pathology; D005910:Glioma / Q000098:blood supply* / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A