Mechanisms of Brain Tumor Angiogenesis

Abstract

The growth of brain tumors is dependent on the development of new vessels, a process called angiogenesis. In the clinic, neovascularization has been used as an independent prognostic marker, and is also a promising therapeutic target for treatments of patients with brain tumors. A large body of evidence demonstrates that brain tumor angiogenesis is an orchestrated process modulated by an array of factors, both pro-angiogenic and anti-angiogenic, in tumors and their microenvironment. Of great interest, vascular endothelial growth factors (VEGF), angiopoietins (Ang), platelet-derived growth factors (PDGF) and their respective receptors as well as hypoxia (low oxygen tensions) and hypoxia-inducible factor-1 (HIF-1) are considered the most critical molecules and agents in modulation of brain tumor angiogenesis. Additional factors such as hepatocyte growth factor (HGF) and its receptor, c-Met, transforming growth factor β (TGF-β), interleukin-8 (IL-8), integrins, and nitric oxide (NO) are also important in brain tumor angiogenesis. This chapter summarizes data from glioma angiogenesis studies, as malignant gliomas count for nearly 40% incidence of brain tumors in humans, and results of these studies should apply to angiogenesis occurring in other types of brain tumors. A better understanding of the complex process of brain tumor angiogenesis will lead to further advances in development of new and more effective drugs and treatment for patients with malignant brain tumors.