Localization of vascular endothelial growth factor-D in malignant melanomasuggests a role in tumour angiogenesis

Expression of angiogenic and lymphangiogenic factors by tumours may influen ce the route of metastatic spread. Vascular endothelial growth factor (VEGF ) is a regulator of tumour angiogenesis, but studies of the inhibition of s olid tumour growth by neutralizing anti-VEGF antibodies indicated that othe r angiogenic factors may be involved. VEGF-D may be an alternative regulato r because like VEGF it is angiogenic and it activates VEGF receptor-2 (VEGF R-2), an endothelial cell receptor which is a key signalling molecule in tu mour angiogenesis, This study reports the generation of monoclonal antibodi es to the receptor-binding domain of VEGF-D and the use of these antibodies to localize VEGF-D in malignant melanoma, VEGF-D was detected in tumour ce lls and in vessels adjacent to immunopositive tumour cells, but not in vess els distant from the tumours, These findings are consistent with a model in which VEGF-D, secreted by tumour cells, activates endothelial cell recepto rs and thereby contributes to the regulation of tumour angiogenesis and pos sibly lymphangiogenesis, In addition, VEGF-D was detected in the vascular s mooth muscle, but not tbe endothelium, of vessels in adult colon. The endot helium of these vessels was negative for VEGFR-2 and VEGFR-3, As VEGF recep tors can be up-regulated on endothelium in response to vessel damage and is chaemia, these findings of a specific localization of VEGF-D in smooth musc le of the blood vessels suggest that VEGF-D produced by vascular smooth mus cle could play a role in vascular repair by stimulating the proliferation o f endothelial cells. Copyright (C) 2000 John Wiley & Sons, Ltd.