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dc.contributor.authorGallicchio, Marisa Aen
dc.contributor.authorKaun, Christophen
dc.contributor.authorWojta, Johannen
dc.contributor.authorBinder, Bernden
dc.contributor.authorBach, Leon Aen
dc.identifier.citationJournal of Cellular Physiology; 197(1): 131-8en
dc.description.abstractUrokinase-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.en
dc.subject.otherCell Movement.drug effects.physiologyen
dc.subject.otherDose-Response Relationship, Drugen
dc.subject.otherEmbryo, Mammalianen
dc.subject.otherEnzyme-Linked Immunosorbent Assayen
dc.subject.otherInsulin-Like Growth Factor Binding Protein 6.metabolismen
dc.subject.otherInsulin-Like Growth Factor I.metabolismen
dc.subject.otherInsulin-Like Growth Factor II.genetics.metabolismen
dc.subject.otherPlasminogen Activator Inhibitor 1.biosynthesisen
dc.subject.otherReceptors, Cell Surface.drug effects.metabolismen
dc.subject.otherReceptors, Urokinase Plasminogen Activatoren
dc.subject.otherTissue Plasminogen Activator.biosynthesis.drug effectsen
dc.subject.otherTumor Cells, Cultureden
dc.subject.otherUrokinase-Type Plasminogen Activator.drug effects.metabolismen
dc.titleUrokinase type plasminogen activator receptor is involved in insulin-like growth factor-induced migration of rhabdomyosarcoma cells in vitro.en
dc.typeJournal Articleen
dc.identifier.journaltitleJournal of cellular physiologyen
dc.identifier.affiliationDepartment of Medicine, University of Melbourne, Austin and Repatriation Medical Centre (Austin Campus), Heidelberg, Victoria, Australiaen
dc.type.austinJournal Articleen
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
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