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PMID: 16389942 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Angiogenesis in gliomas: biology and molecular pathophysiology.

Brain pathology (Zurich, Switzerland) ·Vol. 15 ·No. 4 ·2005-10-00 ·Pages 297-310

Fischer I, Gagner JP, Law M, Newcomb EW, Zagzag D

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.

MeSH Terms
Animals Brain Neoplasms/blood supply,pathology Glioma/blood supply,pathology Humans Hypoxia-Inducible Factor 1, alpha Subunit/metabolism Neovascularization, Pathologic/physiopathology Vascular Endothelial Growth Factor A/metabolism
Chemicals
Hypoxia-Inducible Factor 1, alpha Subunit Vascular Endothelial Growth Factor A
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Fischer Ingeborg
Microvascular and Molecular Neuro-oncology Laboratory, New York University School of Medicine, USA.
Gagner Jean-Pierre
Law Meng
Newcomb Elizabeth W
Zagzag David
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Article Info
Journal
Brain pathology (Zurich, Switzerland)
Abbr.
Brain Pathol
ISSN
1015-6305
DOI
10.1111/j.1750-3639.2005.tb00115.x
Published
2005-10-00
Pages
297-310
Language
English
Region
Switzerland
NLM ID
9216781
PMCID
PMC8096031
Subset
IM
Grants
NCI NIH HHS · R01 CA100426 · United States
External Links
PubMed source DOI: 10.1111/j.1750-3639.2005.tb00115.x PMC Full Text View journal details
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