title: Isolation and molecular characterization of brain microvascular endothelial cells from human brain tumors.
abstract: Brain tumor formation and growth is accompanied by the proliferation and infiltration of blood capillaries. The phenotypes of endothelial cells that make up capillaries are known to differ not only in the tissues in which endothelial cells are located but also as a result of the microenvironment to which they are exposed. For this reason, primary cultures of brain endothelial cells were isolated from human brain tumors removed by surgery and compared with cells from normal tissue. The primary confluent monolayers that grew out of isolated capillary fragments consisted of closely associated, elongated, fusiform-shaped cells. But brain tumor-derived endothelial cells in culture exhibited significantly less expression of endothelial-specific Factor VIII-related antigen compared with cells isolated from normal tissue. Cultured cells that exhibited binding of Ulex europaeus lectin were shown to take up Dil-Ac-Ldl and formed continuous monolayers that were joined together by tight junctions. The cells also exhibited characteristics of the cells of the brain microvasculature in vitro as seen by the presence of large numbers of mitochondria and few pinocytotic vesicles and by the absence of Weibel-Palade bodies within the cells. The expression of vascular cell adhesion molecule-1, E-Selectin, and the tight junction associated protein ZO-1 but not intercellular adhesion molecule-1 was demonstrated by immunohistological staining or reverse transcriptase-polymerase chain reaction methodologies. Comparative studies of these endothelial cells with endothelial cells from normal tissue will be useful for determining and understanding how the blood-brain barrier differs and functions in tumor and healthy tissues and may lead to strategies for brain tumor therapeutic approaches.
authors.affiliation: Institute of Pathology, Uni-Klinik Mainz, University of Mainz, Langenbeckstrasse 1, Germany. unger@pathologie.klinik.uni-mainz.de
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Unger
authors.forename: Jens B
authors.initials: JB
authors.lastname: Oltrogge
authors.forename: Hagen
authors.initials: H
authors.lastname: von Briesen
authors.forename: Britta
authors.initials: B
authors.lastname: Engelhardt
authors.forename: Ulrike
authors.initials: U
authors.lastname: Woelki
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schlote
authors.forename: Rudiger
authors.initials: R
authors.lastname: Lorenz
authors.forename: Hansjurgen
authors.initials: H
authors.lastname: Bratzke
authors.forename: C James
authors.initials: CJ
authors.lastname: Kirkpatrick
mesh_terms: D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply*; D001932:Brain Neoplasms / Q000098:blood supply*; D002232:Carbocyanines / Q000378:metabolism; D002469:Cell Separation; D048429:Cell Size; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D010750:Phosphoproteins / Q000378:metabolism; D037121:Plant Lectins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D062826:Zonula Occludens-1 Protein; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D002232:Carbocyanines; D019040:E-Selectin; D005456:Fluorescent Dyes; D008565:Membrane Proteins; D010750:Phosphoproteins; D037121:Plant Lectins; C569042:TJP1 protein, human; C036850:Ulex europaeus lectins; D019010:Vascular Cell Adhesion Molecule-1; D062826:Zonula Occludens-1 Protein; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1