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At least 109 records · Page 6Linked to original sources
PubMed1999

Localization of syndecan-1 in human gastric mucosa associated with ulceration.

Syndecans, cell surface heparan sulphate proteoglycans, are known to function as cell adhesion molecules and as a co-receptor for heparin-binding growth factors that have important roles in tissue homeostasis and repair, but the localization of syndecans in gastric mucosa and their role in gastric ulcer healing are not known. The licalization of syndecan-1, a subfamily protein of syndecans expressed on epithelial cells, was studied in 12 surgically resected human stomachs containing an ulcer or early scar tissue. Localization of syndecan-1 was detected both by immunohistochemistry and by in situ hybridization In non-ulcer sites of gastric mucosa, syndecan-1 protein was expressed at the basolateral surface of foveolar epithelial cells and the cells of intestinal metaplasia, and at the cell surface of stromal plasma cells. In addition, positive dots of syndecan-1 were found in the cytoplasmic area of parietal cells. Foveolar epithelial cells at active stage ulcer margins showed nearly the same intensity of staining as those at non-ulcer site mucosa. By contrast, enhanced staining was obtained in elongated regenerative foveolar cells at the healing ulcer margins and the early scar tissues. The migrating cells on ulcer floors also expressed syndecan-1 protein. The expression sites of syndecan-1 mRNA mostly coincided with those of syndecan-1 protein. These results suggest that syndecan-1 participates in cell adhesion mainly at the foveolar epithelium and plays a role in the healing of gastric ulcers by interacting with heparin-binding growth factors.

Gastric Mucosa↗
PubMed1997

Reduced expression of syndecan-1 in human hepatocellular carcinoma with high metastatic potential.

Syndecans comprise a gene family of transmembrane proteoglycans that regulate cellular behavior through interactions with various effectors, including heparin-binding growth factors and insoluble matrix components. Syndecan-1, the most extensively studied, localizes in epithelial cells and has been shown to present in normal hepatocytes. However, little is known about the change of syndecan-1 expression in human hepatocellular carcinoma (HCC). We investigated syndecan-1-protein expression by immunohistochemistry in 57 HCC tissue samples. Syndecan-1 gene expression was also determined. Syndecan-1 protein was expressed in cytoplasm and cell membrane of the hepatocytes and in the bile duct epithelial cells of liver with underlying hepatitis and cirrhosis. Conversely, among 57 HCC tissues, 39 HCC (68.4%) showed negative staining; 50% of well-differentiated HCC showed positive staining, whereas 82.4% of poorly differentiated HCC were negative. Loss of syndecan-1-protein expression was more prevalent in HCC with intra-hepatic metastasis (85.2%) than those without metastasis (48.0%). Similarly, syndecan-1 expression was significantly reduced in HCC with extra-hepatic metastasis (91.7%) as compared with the HCC without extra-hepatic metastasis (62.2%). The gene expression of syndecan-1 was significantly lower in HCC tissue than that in non-tumoral liver tissue. In 2 human HCC cell lines with poorly differentiated phenotype, HLE and HLF, syndecan-1 expression was markedly decreased both at the mRNA and the protein levels. These results suggest that the loss of syndecan-1 expression is a characteristic feature of HCC with high metastatic potential.

Antibody Specificity↗
PubMed2007

Mechanical strain induces a persistent upregulation of syndecan-1 expression in smooth muscle cells.

Syndecan-1 belongs to a family of transmembrane proteoglycans, acts as a coreceptor for growth factor binding, as well as cell-matrix and cell-cell interactions, and is induced in smooth muscle cells (SMCs) following balloon catheter injury. In this report, we investigated syndecan-1 expression in SMCs in response to several distinct biomechanical force profiles and the related syndecan shedding response. Syndecan-1 mRNA expression increased in response to 5% and 10% cyclic strain (24 h: 206 +/- 40% and 278 +/- 33%, respectively, P < 0.05) when compared to unstrained controls. When subjected to 10% cyclic strain for periods of up to 48 h, syndecan-1 mRNA levels remained elevated at 294 +/- 31%. Notably, the SMC mechanosensor mechanism remained responsive after an initial 24 h "preconditioning" period, as evident by a fivefold increase in syndecan-1 gene expression following a change in cyclic stress from 10% to 20% (48 h: 516 +/- 55%, P < 0.05). Of note, similar behavior was not observed in an analysis of syndecan-2 mRNA levels. Commensurate with mRNA responses, mechanical stress induced an increase in cell-associated syndecan-1 protein levels with an associated increase in protein shedding. Given the varied functions of syndecan-1, stress-induced effects on SMC syndecan-1 expression and shedding may represent an additional component of the pro-inflammatory, growth-stimulating pathways that are activated in response to changes in the mechanical microenvironment of the vascular wall. Syndecan-1 expression is uniquely influenced by changes in the phase and magnitude of the local stress field.

Aorta↗
PubMed2004

Reduction of syndecan-1 expression in differentiated type early gastric cancer and background mucosa with gastric cellular phenotype.

BACKGROUND: Syndecan-1 is known to play a role as a cell adhesion molecule, similar to E-cadherin, and is associated with the maintenance of epithelial morphology. The purpose of this study was to elucidate the role and alterations of syndecan-1 expression in comparison with those of E-cadherin in different cellular phenotypes of differentiated-type gastric cancers (DGCs). METHODS: A total of 80 DGCs at an early stage, and their adjacent mucosa, were evaluated by both immunohistochemistry and in situ hybridization. Syndecan-1 and E-cadherin were assessed by immunohistochemical staining with an anti-syndecan-1 and an anti-E-cadherin antibody, respectively. Based on immunohistochemistry, DGCs and their surrounding mucosa were divided into four types: gastric type (G-type), ordinary type (O-type), complete-intestinal type (CI-type), and null type. RESULTS: The expression sites of syndecan-1 mRNA mostly coincided with those of syndecan-1 protein. Syndecan-1 expression was significantly lower in G-type cancers (30%) than in O- (81%) and CI-type cancers (92%) ( P = 0.0001 and P = 0.004, respectively), but E-cadherin did not show this result. In addition, syndecan-1 expression was significantly reduced in DGCs comprised partly of poorly differentiated adenocarcinoma or signet-ring cell carcinoma, compared to DGCs demonstrating papillary and/or tubular adenocarcinoma ( P = 0.02). G-type intestinal metaplasia (IM) surrounding the tumors was observed in 21% of G-type cancers, in 0% of O-, and in 10% of CI-type cancers ( P = 0.01; G-type vs O-type). Reduction of syndecan-1 expression was significant in G-type IM (25%) compared to non-G-type IM (75%; P = 0.02). CONCLUSIONS: Syndecan-1 plays a role in the growth of G-type cancers at an early stage compared with E-cadherin changes, and the reduction of syndecan-1 expression in IM surrounding the tumors may influence the growth of G-type cancer.

Adenocarcinoma↗
PubMed1996

Suppression of syndecan-1 expression in endothelial cells by tumor necrosis factor-alpha.

Syndecan-1 is a cell surface proteoglycan that binds extracellular matrix components and modulates the activity of heparin-binding growth factors. The expression of syndecan-1 is modified during development, carcinogenesis, and tissue regeneration. During cutaneous wound healing, syndecan-1 expression is transiently induced in newly-formed capillaries of granulation tissue as well as in proliferating keratinocytes. To study the mechanisms underlying this regulation we investigated the effects of several growth factors/cytokines on syndecan-1 expression in two human cell lines: EA.hy 926 endothelial cells and HaCaT keratinocytes. None of these factors significantly altered syndecan-1 mRNA expression in cultured keratinocytes, but when given to endothelial cells, tumor necrosis factor-alpha (TNF-alpha) specifically and dose-dependently suppressed syndecan-1 expression at both mRNA and protein levels. TNF-alpha reduced the amount of syndecan-1 protein in EA.hy 926 cells in both the presence and absence of serum and, at the same time, induced the expression of intercellular adhesion molecule-1 (ICAM-1). The suppressive effect of TNF-alpha on endothelial syndecan-1 expression was reproducible in in vivo experiments in which TNF-alpha-coated beads were administered directly to healing skin wounds of mice. Data supporting these findings were further obtained by injecting TNF-alpha into an experimental rat granulation tissue model. In this tissue TNF-alpha suppressed syndecan-1 mRNA expression by approximately 80%. These results indicate that TNF-alpha is capable of down-regulating syndecan-1 expression in endothelial cells both in vitro and in vivo and suggest that similar mechanisms may be responsible for the changes in syndecan-1 expression observed during various regenerative, developmental, and malignant processes.

Animals↗
PubMed1997

Syndecan-1 expression is down-regulated during myoblast terminal differentiation. Modulation by growth factors and retinoic acid.

Syndecan-1 is an integral membrane proteoglycan involved in the interaction of cells with extracellular matrix proteins and growth factors. It is transiently expressed in several condensing mesenchymal tissues after epithelial induction. In this study we evaluated the expression of syndecan-1 during skeletal muscle differentiation. The expression of syndecan-1 as determined by Northern blot analyses and immunofluorescence microscopy is down-regulated during differentiation. The transcriptional activity of a syndecan-1 promoter construct is also down-regulated in differentiating muscle cells. The decrease in syndecan-1 gene expression is not dependent on the presence of E-boxes, binding sites for the MyoD family of transcription factors in the promoter region, or myogenin expression. Deletion of the region containing the E-boxes or treatment of differentiating cells with sodium butyrate, an inhibitor of myogenin expression, had no effect on syndecan-1 expression. Basic fibroblast growth factor and transforming growth factor type beta, which are inhibitors of myogenesis, had little effect on syndecan-1 expression. When added together, however, they induced syndecan-1 expression. Retinoic acid, an inducer of myogenesis, inhibited syndecan-1 expression and abolished the effect of the growth factors. These results indicate that syndecan-1 expression is down-regulated during myogenesis and that growth factors and retinoic acid modulate syndecan-1 expression by a mechanism that is independent of myogenin.

Animals↗
PubMed1999

Syndecan-1 expression is induced in the stroma of infiltrating breast carcinoma.

Loss of expression of the heparan sulfate proteoglycan syndecan-1 leads to reduced cell adhesion, increased invasive potential, and dysregulated growth of mammary epithelial cells in vitro. We compared syndecan-1 expression in malignant and nonmalignant breast tissues using immunohisto-chemistry with monoclonal antibody B-B4. Staining for syndecan-1 is greatly diminished on malignant cells within infiltrating ductal carcinomas (n = 20) as compared with ductal epithelium of both normal breast (n = 14) and stromal-epithelial neoplasms (n = 10), which exhibit extensive basolateral epithelial staining. Surprisingly, comparison of malignant and nonmalignant breast tissue also reveals a striking difference in expression of syndecan-1 within the stromal compartment. In infiltrating ductal carcinomas, strong staining for syndecan-1 is present both within the connective tissue and on stromal cell surfaces, whereas syndecan-1 expression is absent in the stroma of both normal breast and stromal-epithelial neoplasms. Because syndecan-1 interacts with heparin-binding growth factors such as FGF-2, accumulation of syndecan-1 within the tumor stroma may contribute to the extensive angiogenesis and stromal proliferation characteristic of infiltrating breast carcinoma. Moreover, the induction of syndecan-1 within the stroma, coupled with the loss of syndecan-1 on malignant cells, suggests that changes in syndecan-1 expression are critical in promoting the metastatic phenotype of infiltrating ductal carcinoma of the breast.

Breast Neoplasms↗
PubMed2005

Prognostic significance of syndecan-1 expression in human endometrial cancer.

BACKGROUND: Syndecan-1 binds to various extracellular matrix components via its heparan sulfate glycosaminoglycans. The aim of this study was to investigate syndecan-1 expression in endometrial cancers. PATIENTS AND METHODS: We investigated the expression of the syndecan-1 core protein by immunohistochemistry in 109 endometrial cancers, and analyzed correlation with various clinicopathological features, including patient outcome. RESULTS: Epithelial syndecan-1 expression was significantly lower in advanced stage, high grade, deep myometrial invasion, cervical involvement, lymph node metastasis, lymph vascular space involvement and positive peritoneal cytology. Stromal syndecan-1 expression was significantly higher in high-grade tumors. The disease-free and overall survival rates of patients exhibiting both low epithelial and high stromal syndecan-1 expression was poor. Multivariate analysis showed that high stromal syndecan-1 expression was an independent prognostic factor for both disease-free and overall survival. Low epithelial syndecan-1 expression was a prognostic factor only in the univariate analysis. CONCLUSIONS: Loss of epithelial syndecan-1 and induction of stromal syndecan-1 expression may be associated with tumor progression. Stromal syndecan-1 expression can serve as an indicator of poor prognosis in patients with endometrial cancer.

Endometrial Neoplasms↗
PubMed2006

Syndecan-1 regulates alphavbeta5 integrin activity in B82L fibroblasts.

B82L mouse fibroblasts respond to fibronectin or vitronectin via a syndecan-1-mediated activation of the alphavbeta5 integrin. Cells attached to syndecan-1-specific antibody display only filopodial extension. However, the syndecan-anchored cells extend lamellipodia when the antibody-substratum is supplemented with serum, or low concentrations of adsorbed vitronectin or fibronectin, that are not sufficient to activate the integrin when plated alone. Integrin activation is blocked by treatment with (Arg-Gly-Asp)-containing peptides and function-blocking antibodies that target alphav integrins, as well as by siRNA-mediated silencing of beta5 integrin expression. In addition, alphavbeta5-mediated cell attachment and spreading on high concentrations of vitronectin is blocked by competition with recombinant syndecan-1 ectodomain core protein and by downregulation of mouse syndecan-1 expression by mouse-specific siRNA. Taking advantage of the species-specificity of the siRNA, rescue experiments in which human syndecan-1 constructs are expressed trace the activation site to the syndecan-1 ectodomain. Moreover, both full-length mouse and human syndecan-1 co-immunoprecipitate with the beta5 integrin subunit, but fail to do so if the syndecan is displaced by competition with soluble, recombinant syndecan-1 ectodomain. These results suggest that the ectodomain of the syndecan-1 core protein contains an active site that assembles into a complex with the alphavbeta5 integrin and regulates alphavbeta5 integrin activity.

Animals↗
PubMed2005

Syndecan-1 expression during the formation of junctional epithelium.

BACKGROUND: Syndecans are cell surface heparan sulfate proteoglycans (PG) which can bind to and modulate the action of growth factors and extracellular matrix components (ECM). Syndecan- 1 has been shown to play important roles during early tooth development and wound healing and repair. Among diverse cells and tissues that comprise the periodontium, the junctional epithelium (JE) constitutes a region of significant anatomic and clinical importance, but the nature of inductive signals and molecules involved in its formation is still unclear. Therefore, this work examines if syndecan-1 is associated with formation of JE, and the distribution of other syndecan family members in the epithelium. METHODS: In situ hybridization and immunohistochemical techniques were performed using oral tissues from 4-day-old to 10-week-old mice to investigate the expression of syndecan- 1, -2, -3 and -4 mRNAs and their corresponding proteins. RESULTS: Based on in situ hybridization experiments, all syndecan mRNAs were detected in sulcular epithelium (SE), gingival epithelium (GE), and JE with varying intensity and distribution. Syndecan-1 immunostaining was localized on the cell surface while that of syndecan-2 did not show clear membrane localization. Our experiments in the developing tooth demonstrated that syndecan-1 protein followed characteristic patterns of expression during JE formation and that immunoreactivity for syndecan-1 protein decreased with age when JE cells underwent terminal differentiation. CONCLUSION: Results of syndecan-1 mRNA and protein expression patterns suggested that this proteoglycan might be an important molecule during the formation of JE.

Ameloblasts↗
PubMed2000

High levels of soluble syndecan-1 in myeloma-derived bone marrow: modulation of hepatocyte growth factor activity.

Syndecan-1 is a heparan sulfate proteoglycan expressed on the surface of, and actively shed by, myeloma cells. Hepatocyte growth factor (HGF) is a cytokine produced by myeloma cells. Previous studies have demonstrated elevated levels of syndecan-1 and HGF in the serum of patients with myeloma, both of negative prognostic value for the disease. Here we show that the median concentrations of syndecan-1 (900 ng/mL) and HGF (6 ng/mL) in the marrow compartment of patients with myeloma are highly elevated compared with healthy controls and controls with other diseases. We show that syndecan-1 isolated from the marrow of patients with myeloma seems to exist in an intact form, with glucosaminoglycan chains. Because HGF is a heparan-sulfate binding cytokine, we examined whether it interacted with soluble syndecan-1. In supernatants from myeloma cells in culture as well as in pleural effusions from patients with myeloma, HGF existed in a complex with soluble syndecan-1. Washing myeloma cells with purified soluble syndecan-1 could effectively displace HGF from the cell surface, suggesting that soluble syndecan-1 can act as a carrier for HGF in vivo. Finally, using a sensitive HGF bioassay (interleukin-11 production from the osteosarcoma cell line Saos-2) and intact syndecan-1 isolated from the U-266 myeloma cell line, we found that the presence of high concentrations of syndecan-1 (more than 3 microg/mL) inhibited the HGF effect, whereas lower concentrations potentiated it. HGF is only one of several heparin-binding cytokines associated with myeloma. These data indicate that soluble syndecan-1 may participate in the pathology of myeloma by modulating cytokine activity within the bone marrow.

Biopsy, Needle↗
PubMed1994

Expression of syndecan-1 is induced by differentiation and suppressed by malignant transformation of human keratinocytes.

Syndecans comprise a family of integral membrane proteoglycans that presumably participate in cell-matrix interactions and the modulation of growth factor response. Expression of syndecan-1, a cell surface proteoglycan that binds basic fibroblast growth factor (bFGF) and extracellular matrix components, was studied in cultured human keratinocytes from the oral mucosa and in tissue sections derived from various epithelia and carcinomas of the head and neck. For the study, polyclonal antibodies were raised against the core protein of human syndecan-1. The affinity-purified antibody (designated anti-P117) was shown to react specifically with syndecan-1. Abundant expression of syndecan-1 was detected in frozen sections of various stratified epithelia as well as in cultured keratinocytes. Keratinocytes located in the spinous cell layers showed intense immunoreactivity for syndecan-1, while basal cells stained rather weakly, suggesting that the expression of syndecan-1 could be stimulated during the differentiation of keratinocytes. Cultured human keratinocytes were induced to terminally differentiate by increasing the extracellular calcium concentration of the medium. Parallel to the induction of involucrin expression, the mRNA levels of syndecan-1 were found to increase, suggesting that syndecan-1 is indeed induced during keratinocyte differentiation. The molecular mass and glycosaminoglycan composition of syndecan-1 did not change markedly during calcium-induced differentiation. Malignant transformation was associated with marked reduction of syndecan-1 expression, based on the immunoreactivity of anti-P117 in frozen sections from squamous cell carcinomas (SCCs) of the head and neck.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Expression of syndecan-1 inhibits cell invasion into type I collagen.

Before cells can invade the extracellular matrix, they must alter their expression of adhesion receptors. Syndecan-1 is a cell surface proteoglycan that binds cells to matrix and undergoes changes in expression during development, during differentiation of some cell types, and following malignant transformation in some tumors. To determine if changes in syndecan-1 expression influence cell invasion, we employed a model system in which human B lymphoid cells invade type I collagen gels. Examination of a panel of cell lines reveals that those lines not expressing syndecan-1 invade and migrate within collagen. In contrast, cell lines expressing syndecan-1 fail to invade. To directly assess the effect of syndecan-1 on invasion, ARH-77 cells, which do not express syndecan-1 and readily invade collagen, were transfected with a cDNA for syndecan-1. The syndecan-1-positive transfectants exhibit a drastically reduced ability to invade as compared to parental cells. This inhibition of invasion by syndecan-1 is reversed by preincubating gels with heparin or by growing cells in chlorate, an inhibitor of glycosaminoglycan sulfation. These results demonstrate that expression of syndecan-1 inhibits cell invasion into collagen and that loss of syndecan-1 expression may be necessary prior to the migration of normal or metastatic cells.

Amino Acid Sequence↗
PubMed2001

Cloning and characterization of human syndecan-3.

Syndecans are cell-surface heparan sulfate proteoglycans, which perform a variety of functions in the cell. Most important, they are co-receptors for growth factors and mediate cell-cell and cell-matrix interactions. Four syndecans (syndecan 1-4) have been described in different species. The aim of this work was the cloning and characterization of human syndecan-3. The human syndecan-3 sequence has high homology to the rat and mouse sequences, with the exception of the 5'-region. Syndecan-3 mRNA is mostly expressed in the nervous system, the adrenal gland, and the spleen. When different cell lines were transiently transfected with full-length syndecan-3 cDNA, it was localized to the membrane and induced the formation of long filopodia-like structures, microspikes, and varicosities. Consequently, the actin cytoskeleton was re-organized, since actin staining was mostly found in the cellular extensions and at the cell periphery, co-localizing with the syndecan-3 staining. The development of the phenotype depended on the presence of sugar chains, as transfected glycosaminoglycan-deficient Chinese hamster ovary (CHO) 745 cells did not show these structural changes, nor did transfected CHO K1 cells in the presence of heparin. The similarity of the cloned DNA sequence with that of other mammalian species and the high expression in the nervous system led us to the assumption that human syndecan-3 could perform comparable functions to those described for syndecan-3 in rat and mouse. Additionally, transient transfection experiments suggest a role of human syndecan-3 in the organization of cell shape by affecting the actin cytoskeleton, possibly by transferring signals from the cell surface in a sugar-dependent mechanism.

Actins↗
PubMed1992

Transient expression of syndecan in mesenchymal cell aggregates of the embryonic kidney.

Induction of the embryonic kidney mesenchyme is followed by formation of cell aggregates which subsequently transform into epithelial tubules. Syndecan, which binds various matrix components and growth factors, is a candidate molecule to be involved in this process. We have analyzed the changes in the expression of syndecan during tubule morphogenesis by using in situ hybridization and slot-blot analysis. The expression pattern of syndecan was compared with the distribution of cell proliferation analyzed by immunohistochemistry. Furthermore, the expression of syndecan during formation of the pretubular aggregates was studied in hanging-drop cultures of experimentally induced mesenchymal cells. Syndecan mRNA was expressed in the metanephric mesenchyme prior to induction, was intensely present during formation of the pretubular cell aggregates, but was lost during maturation of the nephron. Slot-blot analyses of the kidney mesenchymes (11-day kidney) cultured in a transfilter situation with a heterotypic inductor tissue that triggers a complete tubulogenic program in the nephric mesenchyme during the first 24 hr suggested the presence of syndecan mRNA in the uninduced mesenchymes with no change during induction. Expression of mRNA was stimulated later (13-day kidney) followed by subsequent decrease. Immunoisolation of sulfate-labeled syndecan, however, revealed a marked stimulation in the induced kidney mesenchyme during the first 24-hr inductive period when the DNA level still remained constant. In hanging-drop cultures where either induced or uninduced mesenchymal cells were dissociated and reaggregated, syndecan was detected only in the induced and aggregating mesenchymal cells. Double-immunostaining demonstrated a close correlation between syndecan expression and cell proliferation analyzed by bromodeoxyuridine incorporation. Thus, it appears that syndecan expression in the mesenchyme is initially induced post-transcriptionally and later during differentiation at the mRNA level. Syndecan may have a dual function during early kidney morphogenesis; it may be involved in cell aggregation through its adhesive properties, and it may contribute to proliferation of the induced mesenchymal cells by binding growth factors.

Animals↗
PubMed2006

Shift syndecan-2 from RACK1 to caveolin-2 upon transformation with oncogenic ras.

Syndecan-2 was found to detach from RACK1 and associate with caveolin-2 and Ras in cells transformed with oncogenic ras. Most of syndecan-2 from transformed cells was revealed with negligible phosphorylations at tyrosine residues. We experimented with HeLa cells transfected with plasmids encoding syndecan-2 and its mutants (syndecan-2(Y180F), syndecan-2(Y192F), and syndecan-2(Y180,192F)) to provide evidences that PY180 of syndecan-2 is a binding site for RACK1 and is deprived in cells transfected with oncogenic ras. However, in HeLa cells transfected with syndecan-2(Y180F), RACK1 was found to sustain its reactions with syndecan-2 independent of phosphorylation. The finding of syndecan-2 reactive with caveolin-2/Ras suggests the molecular complex most likely to obstruct RACK1 for functional attachment at syndecan-2, as revealed in cells transfected with oncogenic ras. We provided evidences to reinforce the view that molecular rearrangements upon transformation are specific and interesting.

Animals↗
PubMed1999

Antisense inhibition of syndecan-3 expression during skeletal muscle differentiation accelerates myogenesis through a basic fibroblast growth factor-dependent mechanism.

Syndecan-3 is a member of a family of transmembrane proteoglycans that posses highly homologous cytoplasmic and transmembrane domains and function as extracellular matrix receptors and low-affinity receptors for signaling molecules such as basic fibroblasts growth factor (FGF-2). Syndecan-3 is transiently expressed in developing limb bud and absent in adult skeletal muscle. In this study we investigated the expression of syndecan-3 and its role on FGF-2-dependent inhibition of myogenesis. Syndecan-3 expression was down-regulated during skeletal muscle differentiation of C(2)C(12) myoblasts, as determined by Northern blot analyses and immunoprecipitation. To probe the function of syndecan-3 during myogenesis, C(2)C(12) myoblasts were stably transfected with a plasmid coding for antisense syndecan-3 mRNA. The resulting inhibition of syndecan-3 expression caused accelerated skeletal muscle differentiation, as determined by expression of creatine kinase and myosin and myoblast fusion. Expression of a master transcription factor for muscle differentiation, myogenin, was also accelerated in antisense syndecan-3-transfected myoblasts compared with control transfected and wild type cells. Reduced expression of syndecan-3 resulted in a 13-fold decrease in sensitivity to FGF-2-dependent inhibition of myogenin expression. Addition of heparin partially reversed this effect. These results demonstrate that syndecan-3 expression is down-regulated during differentiation and the level of expression of membrane-bound heparan sulfate on myoblast surface is critical for fine modulation of responsiveness to FGF-2. These findings strongly suggest a role for syndecan-3 in regulation of skeletal muscle terminal differentiation.

Animals↗
PubMed2000

Syndecan-2 is involved in the mitogenic activity and signaling of granulocyte-macrophage colony-stimulating factor in osteoblasts.

We previously showed that granulocyte-macrophage colony-stimulating factor (GM-CSF) binds to heparan sulfate proteoglycans expressed at the surface of osteoblastic cells and that the mitogenic activity of this cytokine is dependent on the presence of fully sulfated proteoglycans. In this study, we determined if GM-CSF interacts with syndecans, a family of cell surface heparan sulfate proteoglycans. Human primary osteoblasts were found to express syndecan-2 and -4 but few syndecan-1 transcripts and proteins. Recombinant human GM-CSF coupled to biotin was found to bind to syndecan-2. Immunocytochemical transmission electron microscope analysis showed co-localization of syndecan-2 and GM-CSF at the cell membrane surface. Syndecan-2 also co-localized at the cell surface and co-immunoprecipitated with the GM-CSF receptor alpha chain, suggesting a strong interaction between the cytokine, its receptor, and syndecan-2. Phosphorylation of tyrosine residues in syndecan-2 associated with the alpha chain of the GM-CSF receptor was increased after cell stimulation by GM-CSF. Antisense oligonucleotides that reduced specifically the expression of syndecan-2 inhibited the mitogenic activity of GM-CSF and the activation of extracellular signal-regulated kinase-1 induced by the cytokine. Our results indicate functional interactions between syndecan-2 and GM-CSF in osteoblasts, and we propose that syndecan-2 plays a role as a co-receptor for this cytokine.

Base Sequence↗