Introduction

It is widely accepted that solid tumors must acquire a new blood supply in order to grow beyond a few millimeters in size (Folkman 2002). This concept has stimulated much interest in identifying factors that promote or impede angiogenesis. Proangiogenic cytokines that appear to play a role in human cancer progression include the vascular endothelial growth factor (VEGF) family, fibroblast growth factor (FGF) family, interleukin-8 (IL-8), and platelet-derived growth factor (PDGF) family. Numerous endogenous inhibitors of angiogenesis have also been identified, including thrombospondin-1, angiostatin, and endo-statin. It has also been increasingly recognized that genes implicated in malignant transformation, such as the p53 tumor suppressor or the MYCN oncogene, may play an important role in the regulation of an-giogenesis (Hatzi et al. 2000; Yu et al. 2002). The multiplicity of these factors and their potential interactions, emphasizes the complexity of the regulation of angiogenesis. Patterns of new vessel growth vary in different tumor types, and vary even in tumors of the same type but of different clinical stage or histologic grade. For example,VEGF blockade appears to be less effective in suppressing growth of experimental neu-roblastoma tumors than in parallel models of Wilms' tumor (Kim et al. 2001). In addition, expression of angiogenic factors is increased in neuroblastomas of advanced clinical stage; thus, investigating the specific mechanisms by which neuroblastoma tumors acquire a new blood supply may lead to the identification of potential new targets for treatment of this malignancy.

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