VEGF-D deficiency in mice does not affect embryonic or postnatal lymphangiogenesis but reduces lymphatic metastasis.
Vascular endothelial growth factor-D (VEGF-D) is one of the two ligands of the VEGFR-3 receptor on lymphatic endothelial cells. Gene-silencing studies in mice and Xenopus tadpoles recently showed that the role of endogenous VEGF-D in lymphatic development is moderate. By contrast, exogenous VEGF-D is capable of stimulating lymphangiogenesis. Nonetheless, its endogenous role in pathological conditions remains largely unknown. Hence, we reassessed its role in disease, using Vegf-d(null) mice. Vegf-d(null) mice were generated that, under physiological conditions, displayed normal embryonic and postnatal lymphangiogenesis and lymphatic remodelling, efficient lymphatic functioning and normal health. Vegf-d(null) mice also reponded normally in models of skin wound healing and healing of infarcted myocardium, despite enhanced expression of VEGF-D in these models in wild-type mice. In contrast, Vegf-d(null) mice displayed reduced peritumoral lymphangiogenesis and lymph node metastasis in an orthotopic pancreatic tumour model. Together, our data indicate that endogenous VEGF-D in mice is dispensible for lymphangiogenesis during development, in postnatal and adult physiology and in several pathological conditions, but significantly contributes to lymphatic metastasis.
Koch
Marta
M
Vesalius Research Centre, VIB, B-3000 Leuven, Belgium.
Dettori
Daniela
D
Van Nuffelen
An
A
Souffreau
Joris
J
Marconcini
Lucia
L
Wallays
Goedele
G
Moons
Lieve
L
Bruyère
Françoise
F
Oliviero
Salvatore
S
Noel
Agnes
A
Foidart
Jean-Michel
JM
Carmeliet
Peter
P
Dewerchin
Mieke
M
D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary; D000818:Animals; D004195:Disease Models, Animal; D047108:Embryonic Development / Q000502:physiology; D005260:Female; D018390:Gene Targeting / Q000379:methods; D008113:Liver Neoplasms / Q000378:metabolism; D042583:Lymphangiogenesis / Q000502:physiology*; D008202:Lymphangioma / Q000378:metabolism; D008207:Lymphatic Metastasis / Q000503:physiopathology*; D008208:Lymphatic System / Q000196:embryology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000503:physiopathology; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000378:metabolism; D010641:Phenotype; D012867:Skin / Q000293:injuries; D042643:Vascular Endothelial Growth Factor D / Q000172:deficiency* / Q000502:physiology; D014945:Wound Healing / Q000502:physiology
D042643:Vascular Endothelial Growth Factor D