title: Angiogenetic signaling through hypoxia: HMGB1: an angiogenetic switch molecule.
abstract: The initiation of angiogenesis, called the angiogenetic switch, is a crucial early step in tumor progression and propagation, ensuring an adequate oxygen supply. The rapid growth of tumors is accompanied by a reduced microvessel density, resulting in chronic hypoxia that often leads to necrotic areas within the tumor. These hypoxic and necrotic regions exhibit increased expression of angiogenetic growth factors, eg, vascular endothelial growth factor, and may also attract macrophages, which are known to produce a number of potent angiogenetic cytokines and growth factors. A group of molecules that may act as mediators of angiogenesis are the so-called high-mobility group proteins. Recent studies showed that HMGB1, known as an architectural chromatin-binding protein, can be extracellularly released by passive diffusion from necrotic cells and activated macrophages. To examine the angiogenetic effects of HMGB1 on endothelial cells an in vitro spheroid model was used. The results of the endothelial-sprouting assay clearly show that exogenous HMGB1 induced endothelial cell migration and sprouting in vitro in a dose-dependent manner. Thus, this is the first report showing strong evidence for HMGB1-induced sprouting of endothelial cells.
authors.affiliation: Center for Human Genetics, University of Bremen, Leobenerstr. ZHG, D-28359 Bremen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schlueter
authors.forename: Holger
authors.initials: H
authors.lastname: Weber
authors.forename: Britta
authors.initials: B
authors.lastname: Meyer
authors.forename: Piere
authors.initials: P
authors.lastname: Rogalla
authors.forename: Kerstin
authors.initials: K
authors.lastname: Röser
authors.forename: Sven
authors.initials: S
authors.lastname: Hauke
authors.forename: Jörn
authors.initials: J
authors.lastname: Bullerdiek
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects*; D024243:HMGB1 Protein / Q000494:pharmacology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured
chemical_list: D024243:HMGB1 Protein