Figure 1.

Soluble angiogenic factors are released from tumour cells to induce and regulate key steps in angiogenesis. Many of these factors have also been found to have a role in ocular and, more specifically, corneal neovascularisation. Angiopoietin-1 binds to endothelial Tie-2 receptors to stabilise the established vasculature. Angiopoietin-2, however, which is secreted by tumour cells, and which competes with angiopoietin-1 for the Tie-2 receptor, increases vascular basal membrane degradation and EC migration. Vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF) may also be secreted by tumour cells, and exert pro-angiogenic effects via their respective EC receptors (with VEGF-receptors requiring assistance from neuropilins). Tumours or ECs may also release matrix metalloproteinases (MMPs). These have some pro-angiogenic effects, but also cleave antiangiogenic endostatin from collagen XVIII of the extracellular matrix, and angiostatin from circulating plasminogen (not depicted; adapted from Folkman,¹⁰⁰ with permission from Macmillan Publishers Ltd).