Disease relevance of SDC1

• Cell surface proteoglycan syndecan-1 mediates hepatocyte growth factor binding and promotes Met signaling in multiple myeloma [1].
• In comparison with bile ductular cells of normal liver, reactive ductules in chronic cholestasis were marked by an elevated expression of syndecan-1, surrounded by an increased perlecan expression [2].
• These data reveal changes in the expression of syndecan-1, syndecan-3, and perlecan in human chronic cholestatic liver disease, that may be important in the deposition of matrix components and activation of growth factors that support ductular reaction and accompanying fibrogenesis [2].
• These data reinforce the role of the tumor stroma in ovarian adenocarcinoma and suggest that stromal induction of syndecan-1 contributes to the pathogenesis of this malignancy [3].
• For HPV11 infectivity assays, a high virion inoculum was required to infect K562 cells, whereas ectopic expression of syndecan-1 increased permissiveness eightfold and expression of syndecan-4 or glypican-1 fourfold [4].

High impact information on SDC1

• Physiological degradation converts the soluble syndecan-1 ectodomain from an inhibitor to a potent activator of FGF-2 [5].
• We find that this control can be imposed by the soluble syndecan-1 ectodomain, a heparan sulfate proteoglycan shed from cell surfaces into wound fluids [5].
• The syndecan family of cell-surface heparan sulfate proteoglycans participate in multiple cell behaviors ranging from growth factor signaling to cell adhesion [6].
• Syndecan captures, protects, and transmits HIV to T lymphocytes [7].
• The B lymphocyte-induced maturation protein (Blimp-1) upregulates the expression of syndecan-1 and J chain and represses that of c-myc [8].

Chemical compound and disease context of SDC1

• Porphyromonas gingivalis lipopolysaccharide induces shedding of syndecan-1 expressed by gingival epithelial cells [9].
• The syndecan-1 ectodomain regulates alphavbeta3 integrin activity in human mammary carcinoma cells [10].
• OBJECTIVES: Loss of epithelial heparan sulfate proteoglycan syndecan-1 has been associated with a more aggressive behavior in various cancer forms, but the prognostic significance of syndecan-1 expression in colorectal cancer is unclear [11].
• Reduced syndecan-1 expression stimulates heparin-binding growth factor-mediated invasion in ovarian cancer cells in a urokinase-independent mechanism [12].
• These results suggested that cell surface HS/syndecan-1 has preventive role for calcium oxalate nephrolithiasis via creation of a charge barrier against COM crystal attachment [13].

Biological context of SDC1

• Transient transfection assays, using wild-type and mutant SDC1 promoter-luciferase genes, led to the identification of a nuclear hormone receptor-binding hexad arranged as a direct repeat separated by one nucleotide (DR-1) in the proximal promoter that was necessary and sufficient for activation by FXR [14].
• Cleavage of syndecan-1 by membrane type matrix metalloproteinase-1 stimulates cell migration [15].
• The role of syndecan cytoplasmic domain in basic fibroblast growth factor-dependent signal transduction [16].
• The transmembrane heparan sulfate proteoglycan syndecan-1 was identified from a human placenta cDNA library by the expression cloning method as a gene product that interacts with membrane type matrix metalloproteinase-1 (MT1-MMP) [15].
• The intensity of syndecan-1 staining within the stroma showed generally an inverse correlation with the degree of tumor cell differentiation [17].

Anatomical context of SDC1

• Treatment of human hepatocytes with either naturally occurring (chenodeoxycholic acid) or synthetic (GW4064) FXR ligands resulted in both induction of SDC1 mRNA and enhanced binding, internalization, and degradation of low density lipoprotein [14].
• We speculate that CASK mediates a link between the extracellular matrix and the actin cytoskeleton via its interaction with syndecan and with protein 4 [18].
• Within the immune system, expression of the HSPG syndecan-1 (CD138) is characteristic of terminally differentiated B cells, ie, plasma cells, and their malignant counterpart, multiple myeloma (MM) [1].
• Of the HSPGs, syndecan-1 is the major epithelial form and is strongly upregulated in wound edge keratinocytes [4].
• Syndecan-1 was not detected in normal ovary but was present in the epithelial and stromal cells of benign and borderline tumors and in ovarian adenocarcinomas [3].

Associations of SDC1 with chemical compounds

• Increased expression of SDC1 may account in part for the hypotriglyceridemic effect that can result from the administration of chenodeoxycholic acid to humans [14].
• Specific glycosaminoglycan lyase digestions, followed by product analyses using fluorescence-assisted carbohydrate electrophoresis and immunoprecipitation experiments, showed that the p53 form is associated with syndecan-1 through both chondroitin sulfate and heparan sulfate [19].
• We conclude that ADAMTS-4 activation in this cell system involves the coordinated activity of both glycosylphosphatidyl inositol-anchored MT4-MMP and the proteoglycan form of syndecan-1 on the cell surface [19].
• These results indicate that several HSPGs can serve as HPV receptors and support a putative role for syndecan-1, rather than alpha6 integrin, as a primary receptor protein in natural HPV infection of keratinocytes [4].
• Although the proteolytic cleavage of IGFBP-rP1 decreased its heparin-binding activity, the cleaved form could bind syndecan-1 efficiently [20].
• We propose that tyrosine dephosphorylation of syndecan-1 may regulate its association with cytoskeleton components [21].

Physical interactions of SDC1

• Here we show that RANTES directly binds in a glycosaminoglycan-dependent manner to SD-1, SD-4, and CD44 [22].
• In endothelial culture supernatants, IL-8 was detected in a trimolecular complex with heparan sulfate and syndecan-1 [23].
• Here, we show that recombinant alpha 3 LG4 and a 19-mer synthetic peptide (A3G756) within alpha 3 LG4 active for syndecan binding increased the expression of matrix metalloproteinase-1 (MMP-1) in keratinocytes and fibroblasts [24].
• Here, we show that a recombinant alpha3 LG4 and synthetic peptides containing syndecan binding motif induced a cell motility and a MMP-9 expression in ketarinocytes [25].
• Here we provide evidence that each PDZ domain of syntenin can interact with a syndecan [26].

Enzymatic interactions of SDC1

• Syndecan-1 was thought to be a cell surface receptor for both intact and cleaved IGFBP-rP1 forms [20].

Regulatory relationships of SDC1

• These results suggest that the shedding of syndecan-1 promoted by MT1-MMP through the preferential cleavage of Gly245-Leu246 peptide bond stimulates cell migration [15].
• Thus, current studies demonstrate that hepatic SDC1 is induced in an FXR isoform-specific manner [14].
• In contrast, syndecan-1 shedding induced by 12-O-tetradecanoylphorbol-13-acetate treatment was inhibited by BB-94 but not by either TIMP-1 or TIMP-2 [15].
• CCR5 is therefore involved in the RANTES-induced accelerated shedding of SD-1 and SD-4 ectodomains [22].
• Shedding of syndecan-1 was also induced by MT3-MMP but not by other MT-MMPs [15].

Other interactions of SDC1

• These results support a specific role for shed syndecan-1 or MMP7-syndecan-1 complexes in tumor progression and add to accumulating evidence that syndecans and glypicans have nonequivalent functions in vivo [27].
• Treatment of cells with MMP inhibitor BB-94 or tissue inhibitor of MMP (TIMP)-2 but not TIMP-1 interfered with the syndecan-1 shedding promoted by MT1-MMP expression [15].
• Stromal expression of syndecan-1 and glypican-1 were poor prognostic factors for survival in univariate analysis [3].
• The detection of a variant form of syndecan-3 as a major stromal HSPG suggests a specific role for this syndecan in haemopoiesis [28].
• Furthermore, the close correlation between syndecan expression and negative ER status raises the possibility of hormonal regulation or more likely an association with an aggressive, ER-negative carcinoma phenotype [29].

Analytical, diagnostic and therapeutic context of SDC1

• Western blotting revealed positive bands with all antibodies and Northern blotting for syndecan-1 was also positive [2].
• We evaluated the influence of soluble syndecan-1 and serum bFGF determined by ELISA on outcome in 184 lung cancer patients (non-small cell lung cancer, n = 138; small cell lung cancer, n = 46) [30].
• When recombinant forms of these proteins were added to the cell culture, they induced a concentration-dependent increase in syndecan-1 ectodomain shedding [9].
• Syndecan-1 expression by peripheral blood mononuclear cells (PBMC) from healthy, gingivitis, and chronic periodontitis subjects was assessed by flow cytometry [31].
• Here, we demonstrate the precise localization and order of the human syndecan-1 and N-myc genes using fluorescence in situ hybridization techniques that provide different levels of resolution [32].

References