%0 Journal Article
%T Angiogenic Signalling Pathways Altered in Gliomas: Selection Mechanisms for More Aggressive Neoplastic Subpopulations with Invasive Phenotype
%A Susana Bulnes
%A Harkaitz Bengoetxea
%A Naiara Ortuzar
%A Enrike G. Argando£¿a
%A ¨¢lvaro Garcia-Blanco
%A Irantzu Rico-Barrio
%A Jos¨¦ V. Lafuente
%J Journal of Signal Transduction
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/597915
%X The angiogenesis process is a key event for glioma survival, malignancy and growth. The start of angiogenesis is mediated by a cascade of intratumoural events: alteration of the microvasculature network; a hypoxic microenvironment; adaptation of neoplastic cells and synthesis of pro-angiogenic factors. Due to a chaotic blood flow, a consequence of an aberrant microvasculature, tissue hypoxia phenomena are induced. Hypoxia inducible factor 1 is a major regulator in glioma invasiveness and angiogenesis. Clones of neoplastic cells with stem cell characteristics are selected by HIF-1. These cells, called ¡°glioma stem cells¡± induce the synthesis of vascular endothelial growth factor. This factor is a pivotal mediator of angiogenesis. To elucidate the role of these angiogenic mediators during glioma growth, we have used a rat endogenous glioma model. Gliomas induced by prenatal ENU administration allowed us to study angiogenic events from early to advanced tumour stages. Events such as microvascular aberrations, hypoxia, GSC selection and VEGF synthesis may be studied in depth. Our data showed that for the treatment of gliomas, developing anti-angiogenic therapies could be aimed at GSCs, HIF-1 or VEGF. The ENU-glioma model can be considered to be a useful option to check novel designs of these treatment strategies. 1. Introduction Gliomas are the most common type of primary tumour in the central nervous system. Glioblastomas (GBM) are the malignant form of gliomas (World Health Organization Grade IV), and progress from a lower-grade glioma (secondary GBM) or appear de novo without any preceding tumour (primary GBM). Glioblastomas are strongly angiogenic tumours displaying a high degree of vascular proliferation and endothelial hyperplasia. It is a neoplasia of glial lineage with high proliferative and invasive capacity and may spread to occupy an entire lobe or even a hemisphere of the brain [1]. The growth of the glioblastoma is related to vascular network adaptation due to the increase of the metabolic necessities of neoplastic cells. During the early stages of gliomas, the metabolic demand is supplied by the vast microvasculature of the CNS; however, when the metabolic supply capacity is exceeded during neoplastic progression, new formation of vessels becomes necessary [2¨C4]. The genesis of new vessels from preexisting ones is called angiogenesis, in opposition to vasculogenesis, which refers to the formation of vessels from hematopoietic niches [5, 6]. Angiogenesis is a complex phenomenon, necessary for the progression of malignant gliomas [7]. The start
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