title: Interaction of plasminogen-related protein B with endothelial and smooth muscle cells in vitro.
abstract: Plasminogen-related protein B (PRP-B) closely resembles the N-terminal plasminogen activation peptide, which is released from plasminogen during conversion to plasmin. We have previously demonstrated that the steady-state level of mRNA encoding PRP-B is increased within tumor tissues, and that recombinant PRP-B antagonizes neoplastic growth when administered systemically to mice harboring tumors, but no insights into the cell targets of PRP-B have been presented. Employing serum-free medium optimized for culturing human endothelial or smooth muscle cells, we show that recombinant PRP-B inhibits basic fibroblast growth factor-dependent cell migration for both cell types, as well as tube formation of endothelial cells. Comparison with the angiogenesis inhibitors angiostatin and endostatin revealed similar results. Recombinant PRP-B is effective in promoting cell attachment of endothelial and smooth muscle cells, and antibody interference experiments reveal that the interaction of recombinant PRP-B with endothelial cells is mediated at least in part by alpha(v)-containing integrins. Inhibition of angiogenesis in vivo by PRP-B was demonstrated in the chicken chorioallantoic membrane assay. PRP-B and other antiangiogenic molecules may elicit metabolic perturbations in endothelial cells as well as perivascular mesenchymal cells such as smooth muscle cells and pericytes.
authors.affiliation: Orthopaedic Research Laboratories, Massachusetts General Hospital and Harvard Medical School, GRJ 1124, 55 Fruit Street, Boston, MA 02114, USA.
authors.forename: Hideo
authors.initials: H
authors.lastname: Morioka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Morii
authors.forename: Tikva
authors.initials: T
authors.lastname: Vogel
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Hornicek
authors.forename: Lawrence
authors.initials: L
authors.lastname: Weissbach
mesh_terms: D000818:Animals; D001681:Biological Assay; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004347:Drug Interactions / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D010958:Plasminogen / Q000235:genetics*; D011993:Recombinant Fusion Proteins
chemical_list: D016895:Culture Media, Serum-Free; D039001:Integrin alpha Chains; C118420:PLGLB1 protein, human; D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2; D010958:Plasminogen