Mg. Achen et al., Localization of vascular endothelial growth factor-D in malignant melanomasuggests a role in tumour angiogenesis, J PATHOLOGY, 193(2), 2001, pp. 147-154
Citations number
29
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
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.