title: Localization of vascular endothelial growth factor-D in malignant melanoma suggests a role in tumour angiogenesis.
abstract: 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.
authors.affiliation: Ludwig Institute for Cancer Research, Post Office Box 2008, Royal Melbourne Hospital, Victoria 3050, Australia. Marc.achen@ludwig.edu.au
authors.forename: M G
authors.initials: MG
authors.lastname: Achen
authors.forename: R A
authors.initials: RA
authors.lastname: Williams
authors.forename: M P
authors.initials: MP
authors.lastname: Minekus
authors.forename: G E
authors.initials: GE
authors.lastname: Thornton
authors.forename: K
authors.initials: K
authors.lastname: Stenvers
authors.forename: P A
authors.initials: PA
authors.lastname: Rogers
authors.forename: F
authors.initials: F
authors.lastname: Lederman
authors.forename: S
authors.initials: S
authors.lastname: Roufail
authors.forename: S A
authors.initials: SA
authors.lastname: Stacker
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D003106:Colon / Q000098:blood supply; D016228:Endothelial Growth Factors / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D008545:Melanoma / Q000098:blood supply / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000502:physiology; D042643:Vascular Endothelial Growth Factor D
chemical_list: D000911:Antibodies, Monoclonal; D016228:Endothelial Growth Factors; D017978:Receptors, Growth Factor; D042643:Vascular Endothelial Growth Factor D