title: Ultrastructural localization of the vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) receptor-2 (FLK-1, KDR) in normal mouse kidney and in the hyperpermeable vessels induced by VPF/VEGF-expressing tumors and adenoviral vectors.
abstract: Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) interacts with two high-affinity tyrosine kinase receptors, VEGFR-1 and VEGFR-2, to increase microvascular permeability and induce angiogenesis. Both receptors are selectively expressed by vascular endothelial cells and are strikingly increased in tumor vessels. We used a specific antibody to localize VEGFR-2 (FLK-1, KDR) in microvascular endothelium of normal mouse kidneys and in the microvessels induced by the TA3/St mammary tumor or by infection with an adenoviral vector engineered to express VPF/VEGF. A pre-embedding method was employed at the light and electron microscopic levels using either nanogold or peroxidase as reporters. Equivalent staining was observed on both the luminal and abluminal surfaces of tumor- and adenovirus-induced vascular endothelium, but plasma membranes at interendothelial junctions were spared except at sites connected to vesiculovacuolar organelles (VVOs). VEGFR-2 was also localized to the membranes and stomatal diaphragms of some VVOs. This staining distribution is consistent with a model in which VPF/VEGF increases microvascular permeability by opening VVOs to allow the transendothelial cell passage of plasma and plasma proteins.
authors.affiliation: Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: D
authors.initials: D
authors.lastname: Feng
authors.forename: J A
authors.initials: JA
authors.lastname: Nagy
authors.forename: R A
authors.initials: RA
authors.lastname: Brekken
authors.forename: A
authors.initials: A
authors.lastname: Pettersson
authors.forename: E J
authors.initials: EJ
authors.lastname: Manseau
authors.forename: K
authors.initials: K
authors.lastname: Pyne
authors.forename: R
authors.initials: R
authors.lastname: Mulligan
authors.forename: P E
authors.initials: PE
authors.lastname: Thorpe
authors.forename: H F
authors.initials: HF
authors.lastname: Dvorak
authors.forename: A M
authors.initials: AM
authors.lastname: Dvorak
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002196:Capillaries / Q000378:metabolism; D002199:Capillary Permeability; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply / Q000378:metabolism* / Q000648:ultrastructure; D007678:Kidney Glomerulus / Q000098:blood supply / Q000378:metabolism / Q000648:ultrastructure; D007684:Kidney Tubules / Q000098:blood supply / Q000378:metabolism / Q000648:ultrastructure; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008854:Microscopy, Electron; D009389:Neovascularization, Pathologic; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor
chemical_list: D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor