VEGFR-3 in adult angiogenesis

Vascular endothelial growth factor receptor 3 (VEGFR-3, Flt-4), the recepto r for vascular endothelial growth factors (VEGFs) C and D, is expressed on lymphatic endothelium and may play a role in lymphangiogenesis. In embryoni c life, VEGFR-3 is essential for blood vessel development. The purpose of t his study was to investigate whether VEGFR-3 is also involved in blood vess el angiogenesis in the adult. This was studied in human tissues showing ang iogenesis and in a model of VEGF-A-induced iris neovascularization in the m onkey eye, by the use of immunohistochemistry at the light and electron mic roscopic level. VEGFR-3 was expressed on endothelium of proliferating blood vessels in tumours. In granulation tissue, staining was observed in the pr oliferative superficial zone in plump blood vessel sprouts, in the intermed iate zone in blood vessels and long lymphatic sprouts, and in the deeper fi brous zone in large lymphatics, in a pattern demonstrating that lymphangiog enesis follows behind blood vessel angiogenesis in granulation tissue forma tion. At the ultrastructural level, VEGFR-3 was localized in the cytoplasm and on the cell membrane of endotheliall cells of sprouting blood vessels a nd sprouting lymphatics. In monkey eyes injected with VEGF-A, blood vessel sprouts on the anterior iris surface and pre-existing blood vessels in the iris expressed VEGFR-3. In conclusion, these results support a role for VEG FR-3 and its ligands VEGF-C and/or VEGF-D in cell-to-cell signalling in adu lt blood vessel angiogenesis. The expression of VEGFR-3 in VEGF-A-induced i ris neovascularization and in pre-existing blood vessels exposed to VEGF-A suggests that this receptor and possibly its ligands are recruited in VEGF- A-driven angiogenesis. Copyright (C) 2001 John Wiley & Sons, Ltd.