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Angiogenesis in Gliomas

  • Mujeeburahim Cheerathodi
  • Joseph H. McCartyEmail author
Chapter

Abstract

Malignant brain tumors, including glioblastoma (GBM), display growth, survival, and invasive properties that are coupled to blood vessels and vascular-derived factors. For example, GBM stem cells (GSCs) home to perivascular niches and invasive tumor cells commonly disperse through the brain microenvironment via extracellular matrix (ECM)-rich vascular basement membranes. Anti-vascular agents that target angiogenesis, and particularly those involving vascular endothelial cell growth factor-A (VEGF-A) and its receptors, improve progression-free survival in GBM patients. However, these benefits are often transient due to compensation by alternative angiogenic pathways. The detailed molecular mechanisms that couple GBM cells to blood vessels during tumor growth and progression as well as following anti-angiogenesis therapies are just beginning to be elucidated, with various cytokines, growth factors, and ECM proteins playing important roles. In this review we will highlight molecular pathways that link cerebral blood vessels and GBM cells during tumor growth, progression, and invasion. We will also discuss mechanisms underlying GBM-induced angiogenesis, with a particular focus placed on roles for integrin adhesion receptors and their ECM protein ligands. Therapies that target angiogenesis in GBM and other brain cancers will also be summarized.

Keywords

Brain cancer Glioblastoma Growth factors Integrins Extracellular matrix Invasion Neurovascular unit Vascular niches 

Abbreviations

BBB

Blood–brain barrier

CNS

Central nervous system

EC

Endothelial cell

ECM

Extracellular matrix

EGF

Epidermal growth factor

FGF

Fibroblast growth factor

HGF

Hepatocyte growth factor

GBM

Glioblastoma

GSC

GBM stem cell

IL

Interleukin

MAPK

Mitogen-activated protein kinase

MMP

Matrix metalloproteinase

MRP

Multidrug resistance protein

PDGF

Platelet-derived growth factor

RTK

Receptor tyrosine kinase

TGFβ

Transforming growth factor β

TIMP

Tissue inhibitors of matrix metalloproteinase

VEGF

Vascular endothelial cell growth factor

Notes

Acknowledgments

This research was supported by grant funds awarded to J.H.M. from the National Institutes of Neurological Disease and Stroke (R01NS059876 and R01NS078402) and the National Cancer Institute (P50CA127001). Due to space constraints, we apologize to colleagues in the field for not citing their relevant studies.

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© Springer-Verlag Wien 2014

Authors and Affiliations

  1. 1.Department of Neurosurgery, Unit 1004 S5.8136cUniversity of Texas M.D. Anderson Cancer CenterHoustonUSA

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