KDR and metastatic neoplasm: Binding of the two major isoforms of VEGFA (VEGF165 and VEGF121) to VEGFR-2 and VEGFR-1 on endothelial cells was lowest in primary (localized) tumors, whereas the collective binding of the class 3 Semaphorins to endothelial plexins decreased in primary tumors relative to normal tissue and decreased further in metastatic tumors (Fig. 5a).