Clinical significance of the determination of angiogenic factors

Abstract

INTRODUCTION ANGIOGENIC ACTIVITY is known to depend upon a balance between positive and negative angiogenesis regulators [ 11. The alteration of this balance by mechanisms, such as the induction of vascular endothelial growth factor (VEGF), expression of TP53 or RAS mutations, SRC overexpression, and downregulation of thrombospondin-1 expression by TP53 mutation, can switch the angiogenic phenotype and facilitate the growth of solid tumours [2-51. Currently, measurement of intratumoral microvessel density (IMD) by immunocytochemistry appears to be the most reliable method of measuring angiogenic activity [6]. However, the determination of levels of each endothelial growth regulator in tumour tissues and in serum or urine can provide more information on the angiogenic characteristics of each tumour and might be an alternative method for evaluating angiogenic activity. For example, the level of intratumoral VEGF varies greatly between tumours and can be a valuable prognostic factor [7]. The endogenous angiogenesis inhibitor, angiostatin, which can cause tumour regression in human tumour xenografts models, has been detected in serum [8]. Since the biological properties of each endothelial growth factors is different, it will be of particular importance to know the role of each factor in human tumours. Therefore, we have focused on the determination of angiogenic factors, particularly positive endothelial growth regulators including VEGF, platelet-derived endothelial cell growth factorithymidine phosphorylase (I’D-ECGFITP), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF) and metalloproteinases (MM&), in breast cancer patients. In this article, we review our experience and the most relevant data in the literature on the clinical significance of the determination of these endothelial growth regulators in human tumours.