VEGF-D deficiency in mice does not affect embryonic or postnatal lymphangiogenesis but reduces lymphatic metastasis

• Published in: The Journal of pathology Vol. 219; no. 3; pp. 356 - 364
• Main Authors: Koch, Marta, Dettori, Daniela, Van Nuffelen, An, Souffreau, Joris, Marconcini, Lucia, Wallays, Goedele, Moons, Lieve, Bruyère, Françoise, Oliviero, Salvatore, Noel, Agnes, Foidart, Jean-Michel, Carmeliet, Peter, Dewerchin, Mieke
• Format: Journal Article Web Resource
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.11.2009; Wiley; John Wiley & Sons, Inc
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - secondary; Animals; Biochemistry, biophysics & molecular biology; Biochimie, biophysique & biologie moléculaire; Biological and medical sciences; Cardiology. Vascular system; Coronary heart disease; Disease Models, Animal; Embryonic Development - physiology; Female; gene targeting; Gene Targeting - methods; Heart; Hematologic and hematopoietic diseases; Investigative techniques, diagnostic techniques (general aspects); Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Life sciences; Liver Neoplasms - metabolism; Lymphangiogenesis - physiology; Lymphangioma - metabolism; lymphatic; Lymphatic Metastasis - physiopathology; Lymphatic System - embryology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; mouse; myocardial infarction; Myocardial Infarction - physiopathology; Neoplasm Transplantation; Pancreatic Neoplasms - metabolism; pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Phenotype; Sciences du vivant; Skin - injuries; tumour metastasis; Vascular Endothelial Growth Factor D - deficiency; Vascular Endothelial Growth Factor D - physiology; VEGF-D; wound healing; Wound Healing - physiology; Myocardial infarction; pathology; Targeting; tumour metastasis; Malignant lymphadenopathy; Cardiovascular disease; Myocardial disease; Postnatal; Gene; Genetics; Tumor; Lymphangiogenesis; Cicatrization; Lymphatic system; wound healing; Deficiency; Rodentia; gene targeting; Lymphatic; Malignant hemopathy; VEGF-D; Coronary heart disease; Lymph node metastasis; Vertebrata; Anatomic pathology; Mammalia; Vascular endothelium growth factor; Mouse; Animal; Cancer
• ISSN: 0022-3417; 1096-9896; 1096-9896
• DOI: 10.1002/path.2605

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‐dnull mice. Vegf‐dnull mice were generated that, under physiological conditions, displayed normal embryonic and postnatal lymphangiogenesis and lymphatic remodelling, efficient lymphatic functioning and normal health. Vegf‐dnull 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‐dnull 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. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.