Angiogenesis in Gliomas: Biology and Molecular Pathophysiology

Ingeborg Fischer; Jean‐Pierre Gagner; Meng Law; Elizabeth W Newcomb; David Zagzag

doi:10.1111/j.1750-3639.2005.tb00115.x

. 2006 Apr 5;15(4):297–310. doi: 10.1111/j.1750-3639.2005.tb00115.x

Angiogenesis in Gliomas: Biology and Molecular Pathophysiology

Ingeborg Fischer ^1,^2,³, Jean‐Pierre Gagner ^1,^2,³, Meng Law ^4,^5,⁶, Elizabeth W Newcomb ^2,⁶, David Zagzag ^1,^2,^3,^5,^6,^✉

PMCID: PMC8096031 PMID: 16389942

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 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.

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Angiogenesis in Gliomas: Biology and Molecular Pathophysiology

Ingeborg Fischer

Jean‐Pierre Gagner

Meng Law

Elizabeth W Newcomb

David Zagzag

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Angiogenesis in Gliomas: Biology and Molecular Pathophysiology

Ingeborg Fischer

Jean‐Pierre Gagner

Meng Law

Elizabeth W Newcomb

David Zagzag

Abstract

Full Text

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