title: Leukemia inhibitory factor (LIF) inhibits angiogenesis in vitro.
abstract: Using an in vitro model in which endothelial cells can be induced to invade a three-dimensional collagen gel to form capillary-like tubular structures, we demonstrate that leukemia inhibitory factor (LIF) inhibits angiogenesis in vitro. The inhibitory effect was observed on both bovine aortic endothelial (BAE) and bovine microvascular endothelial (BME) cell, and occurred irrespective of the angiogenic stimulus, which included basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), the synergistic effect of the two in combination, or the tumor promoter phorbol myristate acetate. LIF inhibited bFGF- and VEGF-induced proliferation in BAE and BME cells. In addition, LIF inhibited BAE but not BME cell migration in a conventional two-dimensional assay. Finally, LIF decreased the proteolytic activity of BAE and BME cells and increased their expression of plasminogen activator inhibitor-1. These results demonstrate that LIF inhibits angiogenesis in vitro, an effect that can be correlated with a LIF-mediated decrease in endothelial cell proliferation, migration and extracellular proteolysis.
authors.affiliation: Department of Morphology, University Medical Center, Geneva, Switzerland.
authors.forename: M S
authors.initials: MS
authors.lastname: Pepper
authors.forename: N
authors.initials: N
authors.lastname: Ferrara
authors.forename: L
authors.initials: L
authors.lastname: Orci
authors.forename: R
authors.initials: R
authors.lastname: Montesano
mesh_terms: D000302:Adrenal Cortex / Q000098:blood supply; D000818:Animals; D001011:Aorta; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015870:Gene Expression; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008833:Microcirculation; D016685:Mitomycin / Q000494:pharmacology; D009389:Neovascularization, Pathologic; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis; D014158:Transcription, Genetic; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D016685:Mitomycin; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator