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- W1497807784 abstract "4376 Lipid rafts are membrane micro-domains containing cell signaling molecules which cause an increased cell migration, adhesion, invasion, and tumor metastasis upon their activation. Heparan sulfate proteoglycans (HSPG) are signaling macromolecules present on the cell-surface and in the surrounding extracellular matrix (ECM), and found in lipid rafts. Heparanase (HPSE-1) is a unique ECM degrada tive enzyme cleaving heparan sulfate glycosaminoglycan chains (HS GAG) which are attached to HSPG core proteins. Importantly, changes in HS GAG composition promote an altered cell signaling and biological behavior as well as a relocalization of certain HSPG, mainly cell-surface syndecan-1 (Synd-1). We have examined how HPSE-1 treatment of newly developed, highly brain-metastatic human melanoma cells (70W–SM3) affects lipid raft protein composition using Western blotting analyses of isolated lipid rafts. Our results show a HPSE-1 - mediated increase in phosphorylation of extracellular signal-regulated kinase (pERK) and focal adhesion kinase (pFAK) in lipid raft localization. Equally important, we have demonstrated that HPSE-1 affects lipid raft composition by decreasing Synd-1, therefore regulating HSPG mobility from the detergent-insoluble lipid raft of the cell into the medium. These findings are relevant because they provide first-time evidence that HPSE-1 is involved in a novel mechanism regulating cell signaling and tumorigenesis" @default.
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- W1497807784 date "2006-04-15" @default.
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- W1497807784 title "Heparanase alters lipid raft composition in newly developed, highly brain-metastatic melanoma cells" @default.
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