title: In vitro angiogenesis by human umbilical vein endothelial cells (HUVEC) induced by three-dimensional co-culture with glioblastoma cells.
abstract: Glioblastoma multiforme (GBM) is one of the most highly vascularized of all human tumors. Our objective was to characterize a 3-dimensional (3-D) in vitro angiogenesis model by co-culturing HUVEC and GBM cells, and to study the role of VEGF in mediating capillary tubule formation in this model. HUVEC-coated dextran beads were suspended in fibrin gel with human glioma cells on top. The number of sprouts and the length of the processes were measured. HUVEC can be induced to form sprouts and longer processes with lumens, in co-culture with glioma cells that secrete VEGF. Addition of exogenous VEGF enhances this effect. In the absence of glioma cells, many single HUVEC migrate away from the beads, without significant tubule formation. Hypoxia further stimulated sprout formation by 50-100%. Anti-VEGF neutralizing antibody suppressed HUVEC sprouting by 75% in co-culture with glioma cells. This 3-D in vitro co-culture system provides a robust and useful model for analysis of the major steps of glioma-induced angiogenesis.
authors.affiliation: Department of Neurosurgery, Medical College of Virginia Hospitals, Ambulatory Care Center, Virginia Commonwealth University, 417 North 11th Street, Richmond, VA 23298-0631, USA.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Chen
authors.forename: Andre
authors.initials: A
authors.lastname: Htay
authors.forename: Wagner
authors.initials: W
authors.lastname: Dos Santos
authors.forename: George T
authors.initials: GT
authors.lastname: Gillies
authors.forename: Helen L
authors.initials: HL
authors.lastname: Fillmore
authors.forename: Milton M
authors.initials: MM
authors.lastname: Sholley
authors.forename: William C
authors.initials: WC
authors.lastname: Broaddus
mesh_terms: D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D018920:Coculture Techniques / Q000379:methods; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A