title: VEGF-D deficiency in mice does not affect embryonic or postnatal lymphangiogenesis but reduces lymphatic metastasis.
abstract: 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.
authors.affiliation: Vesalius Research Centre, VIB, B-3000 Leuven, Belgium.
authors.forename: Marta
authors.initials: M
authors.lastname: Koch
authors.forename: Daniela
authors.initials: D
authors.lastname: Dettori
authors.forename: An
authors.initials: A
authors.lastname: Van Nuffelen
authors.forename: Joris
authors.initials: J
authors.lastname: Souffreau
authors.forename: Lucia
authors.initials: L
authors.lastname: Marconcini
authors.forename: Goedele
authors.initials: G
authors.lastname: Wallays
authors.forename: Lieve
authors.initials: L
authors.lastname: Moons
authors.forename: Françoise
authors.initials: F
authors.lastname: Bruyère
authors.forename: Salvatore
authors.initials: S
authors.lastname: Oliviero
authors.forename: Agnes
authors.initials: A
authors.lastname: Noel
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Foidart
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Mieke
authors.initials: M
authors.lastname: Dewerchin
mesh_terms: 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
chemical_list: D042643:Vascular Endothelial Growth Factor D