Involvement of the VEGF-Flt-receptor family in angiogenesis

Abstract

Angiogenesis is important not only in normal embryogenesis, tissue organization and its maintenance but also in pathological processes such as ocular disease in diabetes mellitus and rapid growth of tumors in vivo. Recently, endothelial cell-specific growth factor (VEGF) and its receptors (Flt family) has been characterized, and this ligand-tyrosine kinase receptor is considered to be one of the most important systems involved in angiogenesis. VEGF is induced by a variety of normal or tumor cells under conditions such as hypoxia and hypoglycemia and in the presence of substances such as hormones and growth factors. On the other hand, receptors of the Flt family (Flt-1, KDR/Flk-1, Flt-4) are basically strictly expressed only on vascular endothelial cells with a rare exception. Thus, the stimulation of VEGF-Flt towards angiogenesis is through a paracrine mechanism. A direct involvement of Flt-1 and KDR/Flk-1 in vasculogenesis/angiogenesis has recently been demonstrated by gene targetting studies. Blocking of this system might be a useful tool for suppression of solid tumors in vivo.