Open AccessAngiogenesis in Gliomas: Biology and Molecular Pathophysiology
Author(s) -
Fischer Ingeborg,
Gagner JeanPierre,
Law Meng,
Newcomb Elizabeth W.,
Zagzag David
Publication year - 2005
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2005.tb00115.x
Subject(s) - angiogenesis , glioma , neovascularization , cancer research , vascular endothelial growth factor , biology , tumor progression , hypoxia (environmental) , downregulation and upregulation , hypoxia inducible factors , pathology , medicine , chemistry , cancer , gene , vegf receptors , genetics , organic chemistry , oxygen
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 angio‐poietin‐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)‐1 a 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.