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

J Pathol. 2001 Feb;193(2):147-54. doi: 10.1002/1096-9896(2000)9999:9999<::AID-PATH757>3.0.CO;2-G.


Expression of angiogenic and lymphangiogenic factors by tumours may influence the route of metastatic spread. Vascular endothelial growth factor (VEGF) is a regulator of tumour angiogenesis, but studies of the inhibition of solid tumour growth by neutralizing anti-VEGF antibodies indicated that other angiogenic factors may be involved. VEGF-D may be an alternative regulator because like VEGF it is angiogenic and it activates VEGF receptor-2 (VEGFR-2), an endothelial cell receptor which is a key signalling molecule in tumour angiogenesis. This study reports the generation of monoclonal antibodies 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 cells and in vessels adjacent to immunopositive tumour cells, but not in vessels distant from the tumours. These findings are consistent with a model in which VEGF-D, secreted by tumour cells, activates endothelial cell receptors and thereby contributes to the regulation of tumour angiogenesis and possibly lymphangiogenesis. In addition, VEGF-D was detected in the vascular smooth muscle, but not the endothelium, of vessels in adult colon. The endothelium of these vessels was negative for VEGFR-2 and VEGFR-3. As VEGF receptors can be up-regulated on endothelium in response to vessel damage and ischaemia, these findings of a specific localization of VEGF-D in smooth muscle of the blood vessels suggest that VEGF-D produced by vascular smooth muscle could play a role in vascular repair by stimulating the proliferation of endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / physiology
  • Colon / blood supply
  • Endothelial Growth Factors / metabolism
  • Endothelial Growth Factors / physiology*
  • Female
  • Humans
  • Melanoma / blood supply
  • Melanoma / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Muscle, Smooth, Vascular / metabolism
  • Neovascularization, Pathologic / metabolism*
  • Receptors, Growth Factor / physiology
  • Vascular Endothelial Growth Factor D


  • Antibodies, Monoclonal
  • Endothelial Growth Factors
  • Receptors, Growth Factor
  • Vascular Endothelial Growth Factor D