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Title: Urokinase type plasminogen activator receptor is involved in insulin-like growth factor-induced migration of rhabdomyosarcoma cells in vitro.
Austin Authors: Gallicchio, Marisa A;Kaun, Christoph;Wojta, Johann;Binder, Bernd;Bach, Leon A
Affiliation: Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre (Austin Campus), Heidelberg, Victoria, Australia
Issue Date: 1-Oct-2003
Publication information: Journal of Cellular Physiology; 197(1): 131-8
Abstract: Urokinase-type plasminogen activator (uPA) binds to its receptor, uPAR, on the surface of cancer cells, leading to the formation of plasmin. Rhabdomyosarcoma (RMS) cell lines secrete high levels of insulin-like growth factor II (IGF-II), suggesting autocrine IGFs play a major role in the unregulated growth and metastasis of RMS. In vitro, IGF-II and IGF-I increased migration of RD cells to 124+/-9% (P<0.01) and 131+/-8% (P<0.05) of control, respectively. IGF-II-induced migration was abolished by insulin-like growth factor binding protein-6 (IGFBP-6) (P<0.01), a relatively specific inhibitor of IGF-II, and by plasminogen activator inhibitor type 1 (PAI-1) (P<0.05). Aprotinin, a plasmin inhibitor, and mannosamine, which inhibits the synthesis of glycosylphosphatidylinositol (GPI), thereby preventing anchorage of GPI-linked proteins such as uPAR to the cell membrane, also decreased IGF-II- (P<0.05 for both) but not IGF-I-induced migration. [Arg54,Arg55]IGF-II and [Leu27]IGF-II, which preferentially bind to the IGF-I and IGF-II/mannose-6-phosphate receptors (IGF-II/M6PR), respectively, both induced RD cell migration to 146+/-8% (P<0.01) and 120+/-7% (P<0.05) of control, respectively. An anti-uPAR anti-serum reduced IGF-II- and IGF-I-induced migration (P<0.05 for both). An anti-low density lipoprotein-related protein (LRP) anti-serum reduced IGF-I-induced migration (P<0.05). IGF-I and -II both increased specific 125I-single chain uPA (scuPA) binding to RD cells in a dose-dependent manner (P<0.01). These results suggest involvement of the PA/plasmin system in IGF-induced migration and indicate important roles these systems may have in RMS metastasis.
Gov't Doc #: 12942549
DOI: 10.1002/jcp.10352
Journal: Journal of cellular physiology
Type: Journal Article
Subjects: Aprotinin.metabolism
Cell Movement.drug effects.physiology
Dose-Response Relationship, Drug
Embryo, Mammalian
Enzyme-Linked Immunosorbent Assay
Insulin-Like Growth Factor Binding Protein 6.metabolism
Insulin-Like Growth Factor I.metabolism
Insulin-Like Growth Factor II.genetics.metabolism
Plasminogen Activator Inhibitor 1.biosynthesis
Receptors, Cell Surface.drug effects.metabolism
Receptors, Urokinase Plasminogen Activator
Tissue Plasminogen Activator.biosynthesis.drug effects
Tumor Cells, Cultured
Urokinase-Type Plasminogen Activator.drug effects.metabolism
Appears in Collections:Journal articles

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