Disease relevance of Gpc1

• Heparan sulfate proteoglycans as regulators of fibroblast growth factor-2 signaling in brain endothelial cells. Specific role for glypican-1 in glioma angiogenesis [1].
• In this study we investigated the effects of decreased glypican-1 expression in PANC-1 pancreatic cancer cells [2].
• Mutations in one glypican cause a syndrome of human birth defects, suggesting important roles for these proteoglycans in development [3].
• Expression pattern of glypican-1 mRNA after brain injury in mice [4].

High impact information on Gpc1

• By RT-PCR using degenerate oligonucleotide primers based on the sequence homologies, we isolated mouse cDNA encoding a novel member of the glypican family as well as mouse homologues of glypican and OCI-5 [5].
• Together with glypican (David, G., V. Lories, B. Decock, P. Marynen, J.-J. Cassiman, and H. Van den Berghe. 1990. J. Cell Biol. 111:3165-3176), it defines a family of integral membrane HSPGs characterized by GPI linkage and conserved structural motifs, including a pattern of 14 cysteine residues that is absolutely conserved [6].
• The glypican (Gpc) family of cell surface heparan sulfate proteoglycans are expressed in a tissue-specific and developmentally regulated fashion [7].
• Processing of the recycling proteoglycan glypican-1 involves the release of its heparan sulfate chains by copper ion- and nitric oxide-catalyzed ascorbate-triggered autodegradation [8].
• We have investigated the possibility that APP and APLP2 regulate glypican-1 processing during endocytosis and recycling [8].

Chemical compound and disease context of Gpc1

• These data suggest that glypican-1 plays an important role in the responses of pancreatic cancer cells to heparin-binding growth factors, and documents for the first time that its expression may enhance tumorigenic potential in vivo [2].

Biological context of Gpc1

• Stable transfection of a glypican-1 antisense construct decreases tumorigenicity in PANC-1 pancreatic carcinoma cells [2].
• Glypican-1 belongs to a family of glycosylphosphatidylinositol (GPI)-anchored heparan sulfate proteoglycans (HSPGs) that affect cell growth, invasion, and adhesion [2].
• Effects of syndecan-1 and glypican on muscle cell proliferation and differentiation: implications for possible functions during myogenesis [9].
• The rat glypican gene 3 (Gpc3) was previously assigned to chromosome Xq36 (Shen et al., 1997) [10].
• Because FGF2 is a potent stimulator of skeletal muscle cell proliferation and a strong inhibitor of differentiation, it is likely that changes in syndecan-1 and glypican expression will affect myogenesis as both, in part, regulate FGF-dependent signaling [9].

Anatomical context of Gpc1

• The effect of glypican was specific for APP, as glypican did not inhibit laminin-induced neurite outgrowth [11].
• In gastrulating embryos, gpc-4 is the only glypican expressed in anterior visceral endoderm [12].
• Glypican-1, the first-discovered member of this family, was originally found in cultured fibroblasts, and later shown to be a major proteoglycan of the mature and developing brain [3].
• Glypican-1 was also observed in skeletal and smooth muscle, epidermis, and in the developing tubules and glomeruli of the kidney [3].
• Glypican-1 protein localized strongly to axons and, in the adult, to synaptic terminal fields as well [3].

Associations of Gpc1 with chemical compounds

• We have previously shown that copper ions are required to nitrosylate thiol groups in the core protein of glypican-1, a heparan sulfate-substituted proteoglycan [13].
• Prion, amyloid beta-derived Cu(II) ions, or free Zn(II) ions support S-nitroso-dependent autocleavage of glypican-1 heparan sulfate [13].
• Defective nitric oxide-dependent, deaminative cleavage of glypican-1 heparan sulfate in Niemann-Pick C1 fibroblasts [14].
• Nitration was diminished when heparanase was inhibited with suramin or when Gpc-1 expression was silenced by RNAi [14].
• The results showed that Gpc-1 autoprocessing was defective in these cells and, furthermore, greatly depressed in normal fibroblasts treated with U18666A (3-beta-[2-(diethylamino)ethoxy]androst-5-en-17-one), a compound widely used to induce cholesterol accumulation [14].

Physical interactions of Gpc1

• Glypican bound strongly to the APP affinity column [11].

Regulatory relationships of Gpc1

• Secreted glypican may act to inhibit APP-induced neurite outgrowth in vivo by competing with endogenous proteoglycans for binding to APP [11].

Other interactions of Gpc1

• These results suggest that both syndecan-1 and glypican play pivotal, but different, roles in both muscle cell proliferation and differentiation [9].
• Immunoblots with anti-Delta-heparan sulfate antibody showed that four major species--perlecan, glypican, syndecan-3 and syndecan-4--were transiently up-regulated [15].
• Immunoblot analysis of the proteins released by PI-PLC after heparitinase treatment revealed the presence of a main band of 64 and a faint band of 62 kDa, whereas the sizes of the core proteins for glypican present in the incubation media were 62 and 59 kDa [16].
• Myoblast treatment with each inhibitor affected the deposition and assembly of the ECM constituents glypican, fibronectin, and laminin [17].
• Indirect analysis revealed that in myotubes glypican is present on the cell surface as well as associated with the extracellular matrix (ECM) [16].

Analytical, diagnostic and therapeutic context of Gpc1

• In situ hybridization study showed that glypican-1 mRNA was expressed in the region surrounding necrotic tissue, and that the signal intensity peaked 7 days after the cryo-injury [4].
• Data from reverse transcription PCR revealed that the two stromal cell lines expressed mRNA for glypican and syndecan4 [18].
• Immunoprecipitation of incubation medium obtained from differentiated cells incubated with [35S]sulfate by specific antibodies against glypican isolated from Schwann cells demonstrated that the antisera precipitated an intact HSPG [16].

References