Disease relevance of Sdc1

• Differential regulation of syndecan expression by osteosarcoma cell lines in response to cytokines but not osteotropic hormones [1].
• Emphasis is placed on the important role that syndecan-1 has in regulating the growth of B lymphoid malignancies, particularly multiple myeloma [2].
• This was done by transfection of newborn rat Schwann cells with a plasmid vector bearing the rat syndecan-1 cDNA sequence under transcriptional control of the constitutively active cytomegalovirus promoter, and a neomycin resistance gene [3].
• During the transformation of fat-storing cells into myofibroblasts (the key process in the development of liver cirrhosis), the levels of mRNA for syndecan-1, -3, and -4 remain constant, whereas the amount of syndecan-2 mRNA increases and that for betaglycan decreases [4].
• OBJECTIVE: To examine experimentally the sequential changes in syndecan-1 and fibroglycan messenger RNA (mRNA) expression after acute myocardial infarction [5].

High impact information on Sdc1

• Direct interaction of CASK/LIN-2 and syndecan heparan sulfate proteoglycan and their overlapping distribution in neuronal synapses [6].
• Syndecan-1 expressed in Schwann cells causes morphological transformation and cytoskeletal reorganization and associates with actin during cell spreading [3].
• To investigate the biological functions of transmembrane proteoglycans we have produced clonal cell lines of rat Schwann cells that express the hybrid proteoglycan syndecan-1 [3].
• There was no apparent stable association of cell surface syndecan-1 with focal contact sites, as determined by dual staining with anti-syndecan-1 and anti-vinculin antibodies [3].
• The syndecan-1 expressing cells exhibited significantly enhanced spreading on several different substrata, including fibronectin and laminin, and an altered morphology [3].

Chemical compound and disease context of Sdc1

• In control rats, Adriamycin nephrosis was associated with significantly impaired GBM staining for both HSPG core protein (assessed from BL-31 staining) and HS staining (assessed from JM-403 staining) 12 weeks after disease induction [7].
• To test this hypothesis, we studied the effects of lisinopril (5 mg/kg/24 h) on proteinuria, focal glomerulosclerosis (FGS) and glomerular heparan sulfate (HS) proteoglycan (HSPG) GBM staining in rats with established Adriamycin nephrosis [7].

Biological context of Sdc1

• Quantitative Northern blot analysis of total RNA isolated from VSM cells harvested at different cell densities revealed a decrease in syndecan mRNA levels with increased cell density [8].
• cDNA encoding the core protein of rat syndecan was cloned from a neonatal rat aortic cDNA library by polymerase chain reaction amplification [8].
• Syndecan 4V peptide directly potentiates PKC alpha activity, leading to "superactivation" of the enzyme, apparently through an interaction with its catalytic domain [9].
• In this study we investigated the molecular basis of syndecan endocytosis and its role in FGF2 internalization in endothelial cells [10].
• Northern blot analysis and immunohistochemical staining using antibodies to syndecans showed that syndecan-1 was strongly expressed in the brain and spinal cord of the 10-day rat fetus, and the expression became weak as embryogenesis proceeded [11].

Anatomical context of Sdc1

• We reported previously that syndecan-1 expression by cultured rate vascular smooth muscle cells (VSMCs) is induced by serum- or platelet-derived growth factor (PDGF) [12].
• All four syndecan mRNAs were detected in uninjured rat carotid arteries [12].
• Our previous studies indicated that cell surface proteoglycans were mostly heparan sulfate ones (HSPG) in 20 day-old Sertoli cells [Biochim. Biophys. Acta 1510 (2001) 474] [13].
• Syndecan-1 and -2 mRNAs were increased 30 minutes after stimulation of quiescent rat mesangial cells (RMCs) with serum [14].
• In polarized B lymphoid cells, syndecan-1 is targeted specifically to a discrete membrane domain termed the uropod that is located at the cell's trailing edge [15].

Associations of Sdc1 with chemical compounds

• ARH-77 cells do not adhere to type I collagen and readily invade into collagen gels, but following expression of the transmembrane heparan sulfate proteoglycan syndecan-1, they bind collagen and fail to invade [16].
• In contrast, syndecan-1 mRNA expression in response to serum was completely blocked in the presence of cycloheximide [12].
• Within this functional domain, syndecan-1 promotes cell-cell adhesion and concentration of heparin binding growth factors [15].
• Its cytoplasmic domain contains a central region unlike that of any other vertebrate or invertebrate syndecan core protein with a cationic motif that binds inositol phospholipids [17].
• Despite distinct molecular masses of glypican and syndecan glycosaminoglycans and minor differences in disaccharide composition and sulfation pattern, the overall proportion and distribution of sulfated regions and the affinity for the Hep II domain were similar [18].

Regulatory relationships of Sdc1

• The activity of purified recombinant glutathione S-transferase-tagged syndecan-1 expressed in premalignant epithelial cells confirmed that syndecan-1 bears HS chains that exhibit the rare motif that forms the FGF-binding complex with ectopic FGFR1 [19].
• Of the syndecan family, syndecan-2 is highly expressed on virtually all brain vessels and syndecan-1 and -3 are only present on larger blood vessels [20].

Other interactions of Sdc1

• Surprisingly, cells bearing a chimera composed of the glypican extracellular domain fused to the syndecan transmembrane and cytoplasmic domains bind to collagen but remain invasive, implying that adhesion to collagen is not by itself sufficient to inhibit invasion [16].
• Our data indicated that the regulation of their expression specifically depends on the nature of HSPG and Sertoli cell developmental stage and evidenced a specific PKC regulation of HSPG mRNA expression [13].
• Upon purification and deglycosylation, an antiserum to rat liver HSPGs that reacts primarily with syndecan-2 showed a strong signal corresponding to this protein and three weaker bands that may represent additional syndecans. mRNAs for syndecan-1, -2, and -4 were present in the cultures [14].
• Syndecan-4 (syn-4), a transmembrane heparan sulfate-containing proteoglycan, is unique among the four members of the syndecan family in its specific cellular localization to complex cytoskeletal adhesion sites, i.e., focal adhesions [21].
• Glypican-1, syndecan-1 and -4, potential bFGF coreceptors, are mainly regulated at the transcriptional level [22].

Analytical, diagnostic and therapeutic context of Sdc1

• A reverse transcriptase-polymerase chain reaction technique was developed that enabled us to amplify all four syndecan mRNAs in a single reaction tube and determine relative changes in their expression [12].
• On Northern blots of RNA isolated from cultured VSM cells, a syndecan cDNA probe hybridized to a major RNA species of 2.6 kilobases [8].
• Reverse transcription-linked polymerase chain reaction (RT-PCR) and Northern analysis detected syndecan transcripts in the human osteosarcoma cell lines MG-63, TE-85, SaOS-2, and U2OS; human osteoblast-like cells; rat calvarial osteoblasts; and in human bone [1].
• Western blot analysis of proteoglycans from MG-63 and TE-85 cells detected multiple heparan sulfate proteoglycan core proteins consistent with syndecan expression [1].
• Expression of syndecan-1 was verified by Northern and immunoblot analysis and immunoprecipitation of 35SO4-labeled proteoglycans [3].

References