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PubMed2002

Syndecan-4 modulates focal adhesion kinase phosphorylation.

The cell-surface heparan sulfate proteoglycan syndecan-4 acts in conjunction with the alpha(5)beta(1) integrin to promote the formation of actin stress fibers and focal adhesions in fibronectin (FN)-adherent cells. Fibroblasts seeded onto the cell-binding domain (CBD) fragment of FN attach but do not fully spread or form focal adhesions. Activation of Rho, with lysophosphatidic acid (LPA), or protein kinase C, using the phorbol ester phorbol 12-myristate 13-acetate, or clustering of syndecan-4 with antibodies directed against its extracellular domain will stimulate formation of focal adhesions and stress fibers in CBD-adherent fibroblasts. The distinct morphological differences between the cells adherent to the CBD and to full-length FN suggest that syndecan-4 may influence the organization of the focal adhesion or the activation state of the proteins that comprise it. FN-null fibroblasts (which express syndecan-4) exhibit reduced phosphorylation of focal adhesion kinase (FAK) tyrosine 397 (Tyr(397)) when adherent to CBD compared with FN-adherent cells. Treating the CBD-adherent fibroblasts with LPA, to activate Rho, or the tyrosine phosphatase inhibitor sodium vanadate increased the level of phosphorylation of Tyr(397) to match that of cells plated on FN. Treatment of the fibroblasts with PMA did not elicit such an effect. To confirm that this regulatory pathway includes syndecan-4 specifically, we examined fibroblasts derived from syndecan-4-null mice. The phosphorylation levels of FAK Tyr(397) were lower in FN-adherent syndecan-4-null fibroblasts compared with syndecan-4-wild type and these levels were rescued by the addition of LPA or re-expression of syndecan-4. These data indicate that syndecan-4 ligation regulates the phosphorylation of FAK Tyr(397) and that this mechanism is dependent on Rho but not protein kinase C activation. In addition, the data suggest that this pathway includes the negative regulation of a protein-tyrosine phosphatase. Our results implicate syndecan-4 activation in a direct role in focal adhesion regulation.

Animals↗
PubMed2003

Syndecan-4 modulates basic fibroblast growth factor 2 signaling in vivo.

Syndecan-4 is one of the principal heparan sulfate-carrying proteins on the cell surface. Unlike other members of syndecan family, syndecan-4 mediates phosphatidylinositol 4,5-bisphosphate 2 (PIP(2))-dependent PKC-alpha activation, and overexpression of syndecan-4 in vitro results in enhanced FGF2 signaling. The present study was designed to test the functional effect of increased syndecan-4 expression in endothelial cells in transgenic mice. Several transgenic mice lines expressing syndecan-4 cDNA under control of human endothelial nitric oxide (NO) synthase (eNOS) promoter were generated. Exogenous syndecan-4 was mainly expressed in the heart, brain, and lungs. In particular, the heart demonstrated the greatest increase in the ratio of transgenic-to-native syndecan-4 gene expression. Vessels from the eNOS-syndecan-4 mice demonstrated more pronounced vasodilation to FGF2 but not to VEGF-A(165), sodium nitroprusside, and A 23187 compared with wild-type mice. To elucidate the mechanism of this effect, we measured NO release from primary cardiac endothelial cells isolated from transgenic or wild-type adult mice. Cells from the eNOS-syndecan-4 transgenic mice had a significant increase in FGF2- and VEGF-A(165)-induced NO release compared with endothelial cells from the wild-type mice. However, the absolute magnitude of this increase was higher for FGF2 than VEGF-A(165). In conclusion, enhanced syndecan-4 expression in mouse cardiac endothelial cells results in preferential augmentation of FGF2 but not VEGF-A(165)-induced NO release.

Animals↗
PubMed2005

Focal adhesion kinase regulates syndecan-2-mediated tumorigenic activity of HT1080 fibrosarcoma cells.

Expression of syndecan-2, a transmembrane heparan sulfate proteoglycan, is crucial for the tumorigenic activity in colon carcinoma cells. However, despite the high-level expression of syndecan-2 in mesenchymal cells, few studies have addressed the function of syndecan-2 in sarcoma cells. In HT1080 fibrosarcoma cells, we found that syndecan-2 regulated migration, invasion into Matrigel, and anchorage-independent growth but not cell-extracellular matrix adhesion or proliferation, suggesting that syndecan-2 plays different functional roles in fibrosarcoma and colon carcinoma cells. Consistent with the increased cell migration/invasion of syndecan-2-overexpressing HT1080 cells, syndecan-2 overexpression increased phosphorylation and interaction of focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K), membrane localization of T-lymphoma invasion and metastasis gene-1 (Tiam-1), and activation of Rac. Syndecan-2-mediated cell migration/invasion of HT1080 cells was diminished when (a) cells were cotransfected with nonphosphorylatable mutant FAK Y397F or with other FAK mutants lacking PI3K interactions, (b) cells were treated with a specific PI3K inhibitor, or (c) levels of Tiam-1 were knocked down with small interfering RNAs. Furthermore, expression of several FAK mutants inhibited syndecan-2-mediated enhancement of anchorage-independent growth in HT1080 cells. Taken together, these data suggest that syndecan-2 regulates the tumorigenic activities of HT1080 fibrosarcoma cells and that FAK is a key regulator of syndecan-2-mediated tumorigenic activities.

Cell Line, Tumor↗
PubMed2003

Syndecan-2 is essential for angiogenic sprouting during zebrafish development.

We used a morpholino-based gene-targeting screen to identify a novel protein essential for vascular development using the zebrafish, Danio rerio. We show that syndecan-2, a cell-surface heparan sulfate proteoglycan, is essential for angiogenic sprouting during embryogenesis. The vascular function of syndecan-2 is likely conserved, as zebrafish and mouse syndecan-2 show similar expression patterns around major trunk vessels, and human syndecan-2 can restore angiogenic sprouting in syndecan-2 morphants. In contrast, forced expression of a truncated form of syndecan-2 results in embryos with defects in angiogenesis, indicating that the highly conserved cytoplasmic tail is important for the vascular function of syndecan-2. We further show that vascular endothelial growth factor (VEGF) and syndecan-2 genetically interact in vivo using both gain-of-function and loss-of-function studies in zebrafish. VEGF-mediated ectopic signaling is compromised in syndecan-2 morphants, and ectopic syndecan-2 potentiates ectopic VEGF signaling. Syndecan-2 as a novel angiogenic factor is a potential candidate for use in the development of angiogenesis-based therapies.

5' Untranslated Regions↗
PubMed1990

Binding of human syndecan to extracellular matrix proteins.

We have isolated a cell surface proteoglycan from a human mammary cell line (HBL-100). This proteoglycan was found to be a human equivalent to mouse syndecan, because (i) it has identical biochemical properties with murine syndecan, including size, charge, buoyant density, and glycosaminoglycan composition, (ii) its core protein has identical size with murine syndecan as studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and (iii) the core protein is detected with anti-peptide antibody for the cytoplasmic domain of syndecan. HBL-100 cells also showed high expression of syndecan mRNAs, when probed with mouse syndecan cDNA. The ectodomain of the human syndecan revealed binding to type I collagen fibrils and fibronectin but not to laminin, duplicating the binding properties of murine syndecan. Very interestingly, syndecan did not bind to vitronectin, which is known to contain a heparin binding domain and is one of the major adhesive factors of serum for cultured cells. Syndecans are known to change their glycosaminoglycan composition yielding tissue-type specific polymorphic forms of syndecan (Sanderson, R., and Bernfield, M. (1988) Proc. Natl. Acad. Sci. U. S.A. 85, 9562-9566). The members of this family may thus represent a collection of structurally related matrix receptors that could differ in their interactions due to variation of the ectodomain glycosylation.

Blood Proteins↗
PubMed1994

Molecular cloning and genomic organization of chicken syndecan-4.

We have cloned and determined the genomic organization of the core protein of the chicken transmembrane proteoglycan, syndecan-4. Identification of the initial cDNA was accomplished using polyclonal antibodies directed against the cytoplasmic domain of murine syndecan-1 core protein. The cDNA for chicken syndecan-4 encodes a putative core protein of 197 amino acids which consists of a 19-amino acid signal peptide, a 125-amino acid ectodomain, a 25-amino acid transmembrane domain, and a 28-amino acid cytoplasmic domain. The predicted molecular mass of the mature core protein is 19,639 daltons. The ectodomain of chicken syndecan-4 core protein contains three potential sites for glycosaminoglycan attachment, two sites for N-glycosylation, and lacks a dibasic protease cleavage site proximal to the membrane-spanning region found in other syndecan family members. Comparison of the complete amino acid sequence with human syndecan-4 (amphlican (David, G., van der Schueren, B., Marynen, P., Cassiman, J. J., and van den Berghe, H. (1992) J. Cell Biol. 118, 961-969)) and rat syndecan-4 (ryudocan (Kojima, T., Shworak, N. W., and Rosenberg, R. D. (1992) J. Biol. Chem. 267, 4870-4877)) indicates an overall identity of 58 and 56%, respectively, with a 91 and 92% identity in the highly conserved transmembrane and cytoplasmic domains. The core protein of chicken syndecan-4 synthesized by chicken cells is modified with heparan sulfate side chains yielding a proteoglycan with a molecular mass of > 200 kDa in LMH cells (immortalized male leghorn LM strain hepatocytes) and primary skin fibroblasts. Syndecan-4 isolated from chondrocyte cultures runs as a diffuse band between 100 and 200 kDa. Northern analysis of chicken syndecan-4 indicates three messages with distinct sizes of 0.9, 1.3, and 2.9 kb and a wide mRNA tissue distribution. The chicken syndecan-4 gene is divided into 5 exons encoding distinct regions which contain the signal peptide, the glycosaminoglycan attachment sites, a small spacer of unknown function, the glycosylation sites and the transmembrane and cytoplasmic domains.

Amino Acid Sequence↗
PubMed1993

Expression of syndecan regulates human myeloma plasma cell adhesion to type I collagen.

The syndecans comprise a family of integral membrane proteoglycans that regulate cell behaviors by binding to extracellular matrix and binding growth factors. In mouse blood cells, syndecan expression is restricted to cells of the B-cell lineage where it is expressed by pre-B cells and plasma cells, but is absent from circulating B cells. In the present study, we examined the expression, structure, and function of syndecan on human myeloma cell lines and myeloma patient bone marrow cells. On myeloma cells, syndecan is a small (modal relative molecular mass [M(r)] = 120 Kd) heparan sulfate proteoglycan localized at the cell surface. Syndecan was detected by immunodot blotting on 7 of 10 human myeloma cell lines and by reverse transcriptase polymerase chain reaction on 10 of 14 patient samples. Cell binding assays show that myeloma cells expressing syndecan bind to type I collagen via heparan sulfate chains, while those cell lines not expressing syndecan do not bind to collagen. Furthermore, the cell lines expressing syndecan were negative for CD19 and CD45 staining, indicating that syndecan expression is restricted to tumors having a well-differentiated phenotype. We conclude that syndecan acts as a matrix receptor on human myeloma cells but is not expressed by all tumors, suggesting that syndecan may participate in regulating myeloma cell adhesion to the bone marrow stromal matrix.

Cell Adhesion↗
PubMed2000

Semiquantitative reverse transcription-polymerase chain reaction analysis of syndecan-1 and -4 messages in cartilage and cultured chondrocytes from osteoarthritic joints.

OBJECTIVE: To determine the steady-state of messenger RNA (mRNA) levels of syndecan-1 and syndecan-4 in cartilage samples and chondrocytes derived from human osteoarthritic knee joints. METHODS: Steady-state levels of gene-specific mRNA (relative to beta-actin) were measured by semiquantitative polymerase chain reaction (PCR). RESULTS: RT-PCR allowed detection of syndecan-1 (for the first time) and syndecan-4 in both cartilage samples and articular chondrocytes cultured as primary monolayers. The mRNA levels of syndecan-1 were reduced in cartilage tissue from heavily damaged compared to normal-looking areas whereas those of syndecan-4 were significantly increased. In contrast, the expression of syndecan-1 was higher in cultured chondrocytes derived from the fibrillated osteoarthritic cartilage than in cells obtained from intact cartilage, while the syndecan-4 message levels did not differ between the two sites. CONCLUSION: The expression of the cell-surface syndecans 1 and 4 is altered during the osteoarthritic degradative process of the knee joint. The discoordinate syndecan gene expression, which is probably related to the chondrocyte proliferation and clustering, may contribute to the disorganization of the cartilage and the development of OA processes. Isolation and culturing the chondrocytes as monolayers dramatically change the expression of these genes and cannot reflect the in situ condition.

Actins↗
PubMed1998

Characterization of the high affinity cell-binding domain in the cell surface proteoglycan syndecan-4.

The syndecan family of cell surface proteoglycans regulates cell adhesion via their glycosaminoglycan chains and discrete domains of their core proteins. Core protein domains that are variable between syndecan family members may regulate syndecan-specific associations, thereby endowing individual syndecans with unique functions. A syndecan-4-specific domain has been identified in the extracellular syndecan-4 protein. This region mediates cell adhesion when provided as an artificial substratum and is localized within amino acids 56-109 of the recombinant extracellular protein domain of mouse syndecan-4 (mS4ED) (McFall, A. J., and Rapraeger, A. C. (1997) J. Biol. Chem. 272, 12901-12904). To characterize its interaction with the cell surface, radiolabeled ligand binding studies were performed. A single high affinity interaction, with a dissociation constant of 2 x 10(-9) M, was observed between mS4ED and both human and mouse cells. Both chicken S4ED and mS4ED compete for this interaction, although they are only 34% identical within the cell-binding domain sequence. The extracellular protein domains of syndecan-1, -2, and -3, however, fail to compete. The interaction is also observed with native syndecan-4 shed from cell surfaces. Interestingly, the extracellular protein domain of syndecan-1 also mediates cell adhesion, suggesting a similar but discrete interaction for this family member.

Animals↗
PubMed2005

Plasmin- and thrombin-accelerated shedding of syndecan-4 ectodomain generates cleavage sites at Lys(114)-Arg(115) and Lys(129)-Val(130) bonds.

Syndecans are transmembranous heparan sulfate proteoglycans abundant in the surface of all adherent mammalian cells and involved in vital cellular functions. In this study, we found syndecan-1, -2, -3, and -4 to be constitutively expressed by human umbilical vein endothelial cells. The exposure of the ectodomains of syndecan-1 and -4 to the cell surface and their constitutive shedding into the extracellular compartment was measured by immunoassays. In the presence of plasmin and thrombin, shedding was accelerated and monitored by detection and identification of (35)S-labeled proteoglycans. To elucidate the cleavage site of the syndecan ectodomains, we used a cell-free in vitro system with enzyme and substrate as the only reactants. For this purpose, we constructed recombinant fusion proteins of the syndecan-1 and -4 ectodomain together with maltose-binding protein and enhanced yellow fluorescent protein as reporter proteins attached to the N and C termini via oligopeptide linkers. After protease treatment of the fusion proteins, the electrophoretically resolved split products were sequenced and cleavage sites of the ectodomain were identified. Plasmin generated cleavage sites at Lys(114) downward arrowArg(115) and Lys(129) downward arrowVal(130) in the ectodomain of syndecan-4. In thrombin proteolysates of the syndecan-4 ectodomain, the cleavage site Lys(114) downward arrowArg(115) was also identified. The cleavage sites for plasmin and thrombin within the syndecan-4 ectodomain were not present in the syndecan-1 ectodomain. Cleavage of the syndecan-1 fusion protein by thrombin occurred only at a control cleavage site (Arg downward arrowGly) introduced into the linker region connecting the ectodomain with the enhanced yellow fluorescent protein. Because both plasmin and thrombin are involved in thrombogenic and thrombolytic processes in the course of the pathogenesis of arteriosclerosis, the detachment of heparan sulfate-bearing ectodomains could be relevant for the development of arteriosclerotic plaques and recruitment of mononuclear blood cells to the plaque.

Amino Acid Sequence↗
PubMed2006

Expression of syndecans, cell-cell interaction regulating heparan sulfate proteoglycans, within the human endometrium and their regulation throughout the menstrual cycle.

OBJECTIVE: To evaluate the expression of syndecan-1, -2, -3, and -4 in different phases of eutopic endometrium of normal cycling women. DESIGN: Prospective observational study. SETTING: University-based research center for reproductive medicine. PATIENT(S): Twenty-nine healthy ovulatory volunteers. INTERVENTION(S): mRNA and protein expression of syndecan-1 to -4 in human endometrium. MAIN OUTCOME MEASURE(S): Real-time polymerase chain reaction of syndecan members and further characterization of mRNA expression of syndecan-1 and -4 with multiprobe RNase protection assays of epithelial and stromal cells after purification with antibody-coated magnetic beads. For confirmation of results, protein expression and localization using immunohistochemistry for syndecan-1 and -4 was performed. RESULT(S): All syndecans were expressed within human endometrium. Syndecan-1 and -4 proved to be significantly upregulated in whole endometrium during the secretory phase (2.73-fold and 2.85-fold, respectively). Using multiprobe RNase protection assays, a significant upregulation of mRNA was noted in epithelial cells during the secretory phase for both syndecan-1 and -4 (7.46-fold and 2.52-fold, respectively) and confirmed by immunohistochemistry. CONCLUSION(S): Cycle-dependent expression of syndecan-1 and -4 suggests that these adhesion proteins are involved in the regulation of the cycling endometrium.

Adult↗
PubMed2003

Reduced expression of syndecan-1 correlates with histologic dedifferentiation, lymph node metastasis, and poor prognosis in intrahepatic cholangiocarcinoma.

Syndecan-1, a cell-surface transmembrane heparan sulfate proteoglycan, has been reported to correlate with the biologic behavior of malignant tumors in various organs. We examined the correlation between the expression of syndecan-1 at the protein and mRNA levels and clinicopathologic features of 37 intrahepatic cholangiocarcinomas (ICCs). Noncancerous bile duct epithelial cells showed basolateral membranous expression of syndecan-1, whereas ICC cells showed membranous and also diffuse cytoplasmic expression. In situ hybridization demonstrated a distribution of syndecan-1 mRNA similar to that of the protein in carcinoma tissue, suggesting that syndecan-1 expression in ICC is regulated at the transcriptional level. Reduction of syndecan-1 expression in carcinoma was associated with poor histological differentiation (P <0.01): syndecan-1 expression was intense and extensive in well-differentiated (10 cases) and largely negative or weakly positive in poorly differentiated (13 cases) adenocarcinoma, and its expression in moderately differentiated tumors (14 cases) was intermediate. Patients with ICCs demonstrating negative or weak expression of syndecan-1 frequently had lymph node metastases and had a rather poor prognosis after surgical resection compared with those whose tumors demonstrated moderate or strong expression (P <0.05). However, syndecan-1 expression was not correlated with tumor size, stromal desmoplasia, gross classification, vascular invasion, or perineural invasion. We conclude that expression of syndecan-1 could correlate with some aspects of the biologic behaviors of ICCs and may be a useful prognostic marker.

Aged↗
PubMed2003

Syndecan-1 accumulates in lysosomes of poorly differentiated breast carcinoma cells.

Expression patterns of syndecan-1, the cell surface heparan sulfate proteoglycan (HSPG) predominant on epithelial cells, were analyzed in tissue samples from 30 infiltrating human breast carcinomas and in 9 human breast carcinoma cell lines. Immunohistochemical staining demonstrates that while a subset of the breast carcinomas lose syndecan-1, this proteoglycan is expressed or overexpressed in a majority of the cases. Interestingly, cells in poor grade tumors contain intracellular syndecan-1, an observation that has not been previously described and was thus further investigated. Examination of cultured breast carcinoma cell lines indicates that they also display the phenotype of the syndecan-1 positive tumors and thereby provide a model system for analysis of intracellular syndecan-1. All cell lines examined express syndecan-1, and poorly differentiated lines such as BT549 cells internalize the proteoglycan from the cell surface where it accumulates as intact HSPG in intracellular vesicles. Colocalization studies using fluorescent markers identify these to be lysosomes. This finding is unexpected, as the accepted mechanism for degradation of syndecan HSPG following endocytosis is fragmentation of the protein core and glycosaminoglycan chains in endosomes, followed by delivery of the fragments to lysosomes. Lysosomal inactivation using ammonium chloride demonstrates that well-differentiated lines such as T47D and MCF-7 cells, which maintain the majority of syndecan-1 on their cell surfaces, also target intact constitutively endocytosed syndecan-1 to lysosomes. Taken together, these results suggest that mammary epithelial cells utilize a previously uncharacterized mechanism for syndecan-1 catabolism. In this pathway the proteoglycan remains intact as it passes through the endosomal system, prior to arriving at its site of intracellular degradation in lysosomes.

Animals↗
PubMed2005

Constitutive and accelerated shedding of murine syndecan-1 is mediated by cleavage of its core protein at a specific juxtamembrane site.

Syndecan-1 is a developmentally regulated cell surface heparan sulfate proteoglycan (HSPG). It functions as a coreceptor for a variety of soluble and insoluble ligands and is implicated in several biological processes, including differentiation, cell migration, morphogenesis, and recently feeding behavior. The extracellular domain of syndecan-1 is proteolytically cleaved at a juxtamembrane site by tissue inhibitor of metalloprotease-3 (TIMP-3)-sensitive metalloproteinases in response to a variety of physiological stimulators and stress in a process known as shedding. Shedding converts syndecan-1 from a membrane-bound coreceptor into a soluble effector capable of binding the same ligands. We found that replacing syndecan-1 juxtamembrane amino acid residues A243-S-Q-S-L247 with human CD4 amino acid residues can completely block PMA-induced syndecan-1 ectodomain shedding. Furthermore, using liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS), we identified the proteolytic cleavage site of syndecan-1 as amino acids A243 and S244, generated by constitutive and PMA-induced shedding from murine NMuMG cells. Finally, we show that basal cleavage of syndecan-1 utilizes the same in vivo site as the in vitro site. Indeed, as predicted, transgenic mice expressing the syndecan-1/CD4 cDNA do not shed the syndecan-1 ectodomain in vivo. These results suggest that the same cleavage site is utilized for basal syndecan-1 ectodomain shedding both in vitro from NMuMG and CHO cells and in vivo.

Amino Acid Sequence↗
PubMed1994

Association between syndecan-1 expression and clinical outcome in squamous cell carcinoma of the head and neck.

Syndecans are a family of cell-surface heparan sulphate proteoglycans which are involved in cell-matrix interactions and growth factor binding. Syndecan-1 binds basic fibroblast growth factor (bFGF) and several components of the extracellular matrix. Syndecan-1 expression is induced during keratinocyte differentiation and reduced during the formation of squamous cell carcinomas (SCCs). The purpose of this study was to examine the association of syndecan-1 expression with prognostic factors and clinical outcome in SCC of the head and neck. Frozen sections of 29 primary SCCs were analysed for syndecan-1 expression using immunohistochemical methods. Intermediate or strong staining for syndecan-1 was associated with a smaller primary tumour size (P = 0.0005) and higher histological grade of differentiation (P = 0.006) than negative or weakly positive staining. In a univariate analysis, syndecan-1-positive tumours were associated with higher overall (P = 0.001) and recurrence-free survival (P = 0.003) than those tumours with no or little syndecan-1 expression. The results suggest that syndecan-1 could be an important prognostic factor of SCC of the head and neck. Further studies on the prognostic significance of syndecan-1 expression in SCCs are warranted.

Adult↗
PubMed2003

Syndecan-1 expression in thyroid carcinoma: stromal expression followed by epithelial expression is significantly correlated with dedifferentiation.

AIM: To investigate the expression of syndecan-1 in thyroid neoplasia. Syndecan-1 is a proteoglycan regulating cell adhesion. Previous studies have demonstrated that decreased expression of syndecan-1 is linked to malignant progression. METHODS AND RESULTS: Syndecan-1 expression in thyroid neoplasia was studied immunohistochemically. Syndecan-1 was expressed in stromal cells as well as neoplastic epithelial cells. Stromal syndecan-1 expression was observed more frequently in papillary carcinomas larger than 10 mm in size than in microcarcinomas and in widely invasive than in minimally invasive follicular carcinomas. Furthermore, poorly differentiated carcinomas showed this phenomenon more than well-differentiated carcinomas, but the expression in undifferentiated carcinomas was similar to that of poorly differentiated carcinomas. Epithelial syndecan-1 expression was more frequently observed in anaplastic (undifferentiated) carcinomas than in papillary and follicular carcinomas. No significant difference in epithelial expression was found between well and poorly differentiated carcinomas, but undifferentiated carcinomas expressed epithelial syndecan-1 more frequently than did poorly differentiated carcinomas. CONCLUSIONS: These results are in contrast to those previously reported for carcinomas at other sites. It is suggested that the role of syndecan-1 in thyroid carcinomas might be unique. Stromal syndecan-1 expression followed by its epithelial expression is significantly related to progression, including dedifferentiation of thyroid carcinoma.

Adenocarcinoma↗
PubMed1994

Syndecan-1 expressed in Schwann cells causes morphological transformation and cytoskeletal reorganization and associates with actin during cell spreading.

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. 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. Stably expressing cells were selected by growth in G418. Expression of syndecan-1 was verified by Northern and immunoblot analysis and immunoprecipitation of 35SO4-labeled proteoglycans. The syndecan-1 expressing cells exhibited significantly enhanced spreading on several different substrata, including fibronectin and laminin, and an altered morphology. The enhanced spreading appeared to result from the presence of syndecan-1, based on the observation that anti-syndecan-1 antibodies inhibited the enhanced substratum spreading. There was also a reorganization of cytoskeletal structures and formation of focal adhesions, visualized by anti-vinculin staining, which were absent from control Schwann cells. 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. Colocalization of patches of cell surface syndecan-1 with actin was observed, but only during cell spreading. These findings provide evidence for a role of transmembrane proteoglycans in cellular morphogenesis, and suggest that transient association of syndecans with microfilaments may be an important aspect of their biological function.

Actins↗
PubMed2004

Altered expression of syndecan-1 in prostate cancer.

Syndecan-1 is a cell surface heparan sulfate proteoglycan expressed by epithelial cells. It interacts with growth factors, matrix components, and other extracellular proteins, and is thought to be involved in processes such as cell growth, differentiation and adhesion. The expression of syndecan-1 appears generally downregulated in human carcinomas and in experimental cancer models, whereas transfectional expression of syndecan-1 in cultured cancer cells has been shown to inhibit their growth and other aspects of malignant behavior. These findings suggest that analysis of syndecan-1 expression might be of prognostic value in cancer diagnosis, and studies on some carcinomas indeed point to an inverse correlation between syndecan-1 expression and cancer prognosis. So far, little information has been available on the expression of syndecan-1 in human prostate and prostate disease. We have generated and characterized novel antibodies against syndecan-1 and applied them to immunohistochemical staining of specimens representing normal prostate as well as benign and malignant (n=23) prostate disease. The results indicate that syndecan-1 expression is altered but not uniformly absent in prostate cancer, which is in contrast to the expression of high-molecular-weight cytokeratins. The data initially suggest an inverse correlation between syndecan-1 expression and Gleason grade of the tumor, and warrant a larger study to assess the potential prognostic value of analysing syndecan-1 expression in prostate carcinoma.

Aged↗