Different ways to antiangiogenesis by angiostatin and suramin, and quantitation of angiostatin-induced antiangiogenesis.
Angiogenesis, i.e. sprouting of new vessels, their remodelling and regression, is a prerequisite for growth and differentiation of organs and tissues. It is involved in many pathological processes, particularly growth and metastasis of tumours. Angiostatic therapy is a promising new strategy in the treatment of cancer. Angiogenesis inhibitors could intervene in the different phases of the angiogenic cascade, i.e. migration, proliferation, differentiation and three-dimensional organisation of endothelial cells, to inhibit the generation of tumour vessels. The aim of this study was to explore whether in a previously validated in vitro model for quantitation of angiogenesis the effects of the angiostatic factors angiostatin and suramin can be investigated and quantified. Examination of angiostatin and suramin showed that angiostatin-induced antiangiogenesis resulted in inverse angiogenesis. The addition of suramin initially resulted in increased angiogenesis. However, long-term incubation ultimately led to disintegration of endothelial structures, thus establishing the angiostatic effects of suramin. Antiangiogenesis was not only quantified using the previously validated method. It also lent itself to assessment of the extent of antiangiogenesis within the various phases of the angiogenic cascade. This method may therefore be employed in trial studies of potential angiostatic substances and related cellular mechanisms.