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PubMed2006

Reduced syndecan-1 expression is correlated with the histological grade of malignancy at the deep invasive front in oral squamous cell carcinoma.

BACKGROUND: Although many histopathological characteristics of oral squamous cell carcinoma (O-SCC) have been identified as prognostic factors, no factor is completely accurate and unequivocal. This study evaluated the association between the loss of syndecan-1 expression and the histological grade of malignancy at the deep invasive front in O-SCC. METHODS: The expression of syndecan-1 at the invasive tumor front of O-SCC was examined immunohistochemically using archived tissue from 72 cases. The mean age of the patients was 62.5 years (range: 23-90 years) and the male-female ratio was 1.3:1 (41 men, 31 women). There were 26, 24, 11, and 11 cases classified as stages I-IV respectively. The correlation between the intensity of syndecan-1 immunostaining and the clinicopathological factors, especially the histological grade of malignancy at the deep invasive front (invasive front grade) was analyzed. RESULTS: Of the 72 cases, seven (9.7%), 29 (40.3%), 36 (50.0%) showed strong, intermediate, and weak or negative syndecan-1 staining respectively. There were significant differences between syndecan-1 expression and prognosis, differentiation, and pattern of invasion at the deep invasive front. Moreover, the invasive front grade scores, based on the intensity of syndecan-1 staining, were 5.6 +/- 1.0, 8.0 +/- 2.1, and 10.2 +/- 2.3 points with strong, intermediate, and weak or negative intensity respectively; and the difference was significant (P < 0.0001). Patients with intermediate or strong intensity for syndecan-1 had significantly better prognoses than did those with negative or weak intensity (P = 0.0138). CONCLUSION: This study demonstrated that the reduced expression of syndecan-1 seems to be a useful marker of histological malignancy at the deep tumor invasive front and may be a useful prognostic factor in O-SCC.

Adult↗
PubMedDate not supplied

Expression of oncofetal fibronectin and syndecan-1 mRNA in 18 human lung cancer cell lines.

It has been suggested that fibronectin (FN) and syndecan play an important role in many aspects of cell-substrate interactions including cell adhesion. We hypothesized that oncofetal FN (onfFN) and syndecan play an important role in the process of adhesion of several human lung cancer cell lines. To test this, levels of onfFN in the culture supernatant were measured by an enzyme-linked immunosorbent assay in 18 human lung cancer cell lines. In addition, expressions of onfFN and syndecan-1 mRNA were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Of 18 lung cancer cell lines, 3 cell lines (all adenocarcinoma) released a significant amount of onfFN in culture supernatants. Of the 18 cell lines tested, 6 cell lines expressed a significant amount of mRNA for onfFN and 4 expressed a significant amount of mRNA for syndecan-1. Levels of onfFN and expressions of mRNA for onfFN and syndecan-1 were consistently higher in non-small cell lung cancer cell lines than in small cell lung cancer cell lines. In addition, cell lines that expressed mRNA for onfFN and syndecan-1 tended to adhere to culture dishes. Syndecan-1 expression was significantly higher in attached cells compared with nonattached cells within the same cell line. Differences in onfFN and syndecan synthesis may explain some in vitro and in vivo characteristics of lung cancer.

Cell Adhesion↗
PubMed2002

Cell surface proteoglycan syndecan-1 mediates hepatocyte growth factor binding and promotes Met signaling in multiple myeloma.

Heparan sulfate proteoglycans (HSPGs) play a crucial role in growth regulation by assembling signaling complexes and presenting growth factors to their cognate receptors. 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). This study explored the hypothesis that syndecan-1 might promote growth factor signaling and tumor growth in MM. For this purpose, the interaction was studied between syndecan-1 and hepatocyte growth factor (HGF), a putative paracrine and autocrine regulator of MM growth. The study demonstrates that syndecan-1 is capable of binding HGF and that this growth factor is indeed a potent stimulator of MM survival and proliferation. Importantly, the interaction of HGF with heparan sulfate moieties on syndecan-1 strongly promotes HGF-mediated signaling, resulting in enhanced activation of Met, the receptor tyrosine kinase for HGF. Moreover, HGF binding to syndecan-1 promotes activation of the phosphatidylinositol 3-kinase/protein kinase B and RAS/mitogen-activated protein kinase pathways, signaling routes that have been implicated in the regulation of cell survival and proliferation, respectively. These results identify syndecan-1 as a functional coreceptor for HGF that promotes HGF/Met signaling in MM cells, thus suggesting a novel function for syndecan-1 in MM tumorigenesis.

Cell Division↗
PubMed2004

Fibroblast growth factor 2 endocytosis in endothelial cells proceed via syndecan-4-dependent activation of Rac1 and a Cdc42-dependent macropinocytic pathway.

Full activity of fibroblast growth factors (FGFs) requires their internalization in addition to the interaction with cell surface receptors. Recent studies have suggested that the transmembrane proteoglycan syndecan-4 functions as a FGF2 receptor. In this study we investigated the molecular basis of syndecan endocytosis and its role in FGF2 internalization in endothelial cells. We found that syndecan-4 uptake, induced either by treatment with FGF2 or by antibody clustering, requires the integrity of plasma membrane lipid rafts for its initiation, occurs in a non-clathrin-, non-dynamin-dependent manner and involves Rac1, which is activated by syndecan-4 clustering. FGF2 was internalized in a complex with syndecan-4 in 70 kDa dextran-containing endocytic vesicles. FGF2 and syndecan-4 but not dextran endocytosis were blocked by the dominant negative Rac1 while amiloride and the dominant-negative Cdc42 blocked internalization of dextran in addition to FGF2 and syndecan-4. Taken together, these results demonstrate that FGF2 endocytosis requires syndecan-4 clustering-dependent activation of Rac1 and the intact CDC42-dependent macropinocytic pathway.

Animals↗
PubMed1994

The cytoplasmic domain of syndecan-1 is not required for association with Triton X-100-insoluble material.

Cell surface heparan sulfate proteoglycans such as syndecan-1 bind various extracellular matrix proteins and have been suggested to interact with the cytoskeleton. Such interactions are thought to be important for stabilizing cell morphology. Syndecan-1 resists extraction with Triton X-100. This insolubility was reported not to be affected by removal of the glycosaminoglycan chains, suggesting that the insolubility is not due to binding to the extracellular matrix, but rather to an association with the actin cytoskeleton (Rapraeger, A., Jalkanen, M. and Bernfield, M. (1986) J. Cell Biol. 103, 2683-2696). To examine further the interaction of syndecan-1 with the Triton X-100-insoluble residue, we expressed wild-type mouse syndecan-1 and a cytoplasmic deletion mutant (tail-less) in Chinese hamster ovary cells. We observed that both the wild-type and the tail-less syndecan-1 were partly insoluble in Triton X-100. The insolubility was not affected by increasing temperature (37 degrees C or 50 degrees C) or by cytochalasin D. Removal of the glycosaminoglycan chains from the ectodomain, however, resulted in complete Triton X-100 solubility, unlike previous reports. Syndecan-1 could also be released into the Triton X-100-soluble fraction by addition of heparin or heparan sulfate to the extraction medium. We conclude that the cytoplasmic domain of syndecan-1 is not responsible for Triton X-100 insolubility. Instead, our results indicate that Triton X-100 insolubility is caused by an interaction of syndecan-1 molecules with other cellular and/or extracellular molecules mediated by the heparan sulfate chains.

Animals↗
PubMed1996

Syndecan-1 expression in mammary epithelial tumor cells is E-cadherin-dependent.

E-cadherin is a Ca(2+)-dependent cell-cell adhesion molecule, which is mainly expressed in epithelial cells. Recent studies have shown that E-cadherin has an important role as an invasion suppressor molecule in epithelial tumor cells. Syndecan-1 is a cell surface proteoglycan that has been implicated in a number of cellular functions including cell-cell adhesion, cell-matrix anchorage and growth factor presentation for signalling receptors. Its suppression has also been shown to be associated with malignant transformation of epithelial cells. In order to better understand the coordinated regulation of cell-cell and cell-matrix interactions during malignant transformation, we have studied the expression of syndecan-1 in malignant mammary tumor cells genetically manipulated for E-cadherin expression. In invasive NM-e-ras-MAC1 cells, where E-cadherin was partially downregulated by specific antisense RNA, syndecan-1 expression was suppressed. Furthermore, transfection of E-cadherin cDNA into invasive NM-f-ras-TD cells resulted in the upregulation of syndecan-1 expression in association with decreased invasiveness. In both cases, regulation of syndecan-1 occurred post-transcriptionally, since syndecan-1 mRNA levels remained unchanged. Instead, a translational regulation is suggested, since syndecan-1 core protein synthesis was E-cadherin dependent. Another cell adhesion protein, beta 1-integrin was not affected by E-cadherin expression. The data provide an example of coordinated changes in the expression of two cell adhesion molecules, syndecan-1 and E-cadherin during epithelial cell transformation.

Animals↗
PubMed1996

The role of syndecan-1 in malignancies.

Syndecans form a family of cell surface proteoglycans, which can interact with various effector molecules, such as extracellular matrix (ECM) molecules and growth factors. Syndecan-1 is the most extensively studied member of the syndecan family. It is found mainly in epithelial cells, but its expression is developmentally regulated during embryonic development. It has been shown to mediate cell adhesion to several ECM molecules, and to act as a coreceptor for fibroblast growth factors, potent angiogenic growth factors involved also in differentiation. Syndecan-1 expression is reduced during malignant transformation of various epithelia, and this loss correlates with the histological differentiation grade of squamous cell carcinomas, lacking from poorly differentiated tumours. In squamous cell carcinomas of the head and neck, positive syndecan-1 expression correlates with a more favourable prognosis. Recent experimental studies on the role of syndecan-1 in malignant transformation have shown that syndecan-1 expression is associated with the maintenance of epithelial morphology, anchorage-dependent growth and inhibition of invasiveness in vitro. This review will focus on the biological role of syndecan-1 in normal epithelial differentiation and malignant transformation.

Biomarkers, Tumor↗
PubMed2005

Syndecan-1 and E-cadherin expression in differentiated type of early gastric cancer.

AIM: To elucidate the role and alterations of syndecan-1 and E-cadherin expression in different cellular phenotypes of differentiated-type gastric cancers (DGCs). METHODS: A total of 120 DGCs at an early stage, and their adjacent mucosa, were studied both by immunohistochemistry. Syndecan-1 and E-cadherin were assessed by immunohistochemical staining with anti-syndecan-1 and anti-E-cadherin antibodies, 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 (N-type). RESULTS: Syndecan-1 expression was significantly lower in G-type cancers (29.4%) than in O-type (79.6%) and CI-type cancers (90%) (P<0.05, 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<0.05). G-type intestinal metaplasia (IM) surrounding the tumors was observed in 23.8% of G-type, 4.9% of O-type, and 6.7% of CI-type cancers (P<0.05; 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<0.05). CONCLUSION: Loss of syndecan-1 plays a role in the growth of G-type cancers of DGCs at an early stage, and the reduction of syndecan-1 expression in IM surrounding the tumors may influence the growth of G-type cancer.

Adenocarcinoma↗
PubMed2000

Syndecan-1 is targeted to the uropods of polarized myeloma cells where it promotes adhesion and sequesters heparin-binding proteins.

Syndecan-1 (CD138) is a heparan sulfate-bearing proteoglycan present on the surface of myeloma cells where it mediates myeloma cell-cell and cell-extracellular matrix adhesion. In this study, we examined myeloma cell lines for cell membrane localization of syndecan-1. On some cells we note a striking localization of syndecan-1 to a single small membrane protrusion, with the remainder of the cell surface being mostly negative for syndecan-1. Examination of cell morphology reveals that a proportion of cells from myeloma cell lines, as well as primary myeloma cells, are polarized, with a uropod on one end and lamellipodia on the other end. On these polarized cells, syndecan-1 is specifically targeted to the uropod, but in contrast, on nonpolarized cells syndecan-1 is evenly distributed over the entire cell surface. In addition to syndecan-1, several other cell surface molecules localize specifically to the uropod, including CD44 and CD54. Functional assays reveal that myeloma cell lines with a high proportion of polarized cells have a much higher migratory potential than cell lines with few polarized cells. Moreover, the uropod is the cell pole preferentially involved in aggregation of myeloma cells and in adhesion of myeloma cells to osteoblast-like cells. When polarized myeloma cells are incubated with heparin-binding proteins, like hepatocyte growth factor or osteoprotegerin, they concentrate in the uropod. These data indicate that syndecan-1 is targeted to the uropod of polarized myeloma cells and that this targeting plays a role in promoting cell-cell adhesion and may also regulate the biological activity of heparin-binding cytokines.

Animals↗
PubMed2002

Soluble syndecan-1 and serum basic fibroblast growth factor are new prognostic factors in lung cancer.

Syndecan-1 is a ubiquitous and multifunctional extracellular matrix proteoglycan,which mediates basic fibroblast growth factor (bFGF) binding and activity. Shedding of syndecan-1 ectodomain from the plasma membrane is highly regulated. 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). Serum syndecan-1 and bFGF levels were determined from sera taken before treatment. The median follow-up of the patients alive (n = 21) was 8.1 years (range, 6.6-8.9 years). High serum syndecan-1 and bFGF levels tended to occur in the same patients (P = 0.044). When the serum values corresponding to the highest tertile were used as the cutoff value, the median survival time of the patients with a high serum syndecan-1 level (>59 ng/ml) was 4 months [95% confidence interval (CI), 3-6 months] as compared with 11 months (9-16 months) among those with lower serum levels (P = 0.0001), and the median survival time of the patients with a high bFGF level (>3.4 pg/ml) was 5 months (3-8 months) versus 11 months (8-14 months) in those with a lower level (P = 0.023). In general, the prognostic influence of both factors was independent of the histological subtype. Both serum syndecan-1 level (relative risk, 1.8; 95% CI, 1.1-3.1) and serum bFGF level (relative risk, 1.6; 95% CI, 1.0-2.7) had independent influence on survival in a multivariate survival analysis in non-small cell lung cancer. We conclude that high serum syndecan-1 and bFGF levels at diagnosis are associated with poor outcome in lung cancer.

Adult↗
PubMed1993

Organization and promoter activity of the mouse syndecan-1 gene.

Syndecan-1, the prototype of a family of heparan sulfate-containing integral membrane proteoglycans, associates extracellularly with a variety of matrix molecules and growth factors and intracellularly with the actin cytoskeleton. Expressed constitutively on epithelia in mature tissues and in a developmentally regulated manner on epithelial and induced mesenchymal cells during embryogenesis, syndecan-1 appears to be involved in controlling the shape and organization of cells and tissues. To better understand the function and regulation of syndecan-1, we determined the structure of the mouse syndecan-1 gene (Synd-1). Synd-1 is approximately 19.5 kilobases in size and is organized into five exons that appear conserved in other family members. Exon 1 encodes the signal peptide; exon 2, the N-terminal glycosaminoglycan attachment region; exon 3, the bulk of the extracellular domain; exon 4, the protease-susceptible site; and exon 5, the transmembrane and cytoplasmic domains which are highly homologous between syndecan family members. Synd-1 has three transcriptional start sites, two polyadenylation sites, and is not alternatively spliced to produce its 2.6- and 3.4-kilobase mRNA species. Upstream sequences have promoter activity and contain TATA and CAAT boxes as well as a variety of other potential binding sites for transcription factors, including Sp1 (GC box), NF-kappa B, MyoD (E box), and Antennapedia. The structure of the promoter region suggests that control of Synd-1 expression is both constitutive and developmentally regulated. Because Synd-1 exons encode discrete functional domains of the syndecan-1 protein that are conserved throughout the syndecan family, all syndecan genes are likely derived from a common ancestor.

Amino Acid Sequence↗
PubMed1996

Inhibition of in vitro limb cartilage differentiation by syndecan-3 antibodies.

The transmembrane heparan sulfate proteoglycan syndecan-3 is transiently expressed in high amounts during the cellular condensation process that characterizes the onset of limb cartilage differentiation. During condensation, limb mesenchymal cells become closely juxtaposed and undergo cell-cell and cell-matrix interactions that are necessary to trigger cartilage differentiation and cartilage-specific gene expression. To test directly the possible involvement of syndecan-3 in regulating the onset of limb chondrogenesis, we examined the effect of polyclonal antibodies against a syndecan-3 fusion protein on the chondrogenic differentiation of chick limb mesenchymal cells in micromass culture. Syndecan-3 antiserum elicits a dose-dependent inhibition of the accumulation of Alcian blue-stainable cartilage matrix by high density limb mesenchymal cell micromass cultures (2 x 10(5) cells/10 microliters) and a corresponding reduction in steady-state levels of mRNAs for cartilage-characteristic type II collagen and the core protein of the cartilage proteoglycan aggrecan. In preimmune serum-treated control cultures proliferating cells are limited to the periphery of areas of cartilage matrix deposition, whereas large numbers of proliferating cells are uniformly distributed throughout the undifferentiated cultures supplemented with syndecan-3 antiserum. Limb mesenchymal cells cultured at lower densities (1 x 10(5) cells/10 microliters) in the presence of preimmune serum form extensive precartilage condensations characterized by the close juxtaposition of rounded cells by day 2 of culture. In contrast, in the presence of syndecan-3 antiserum, the cells fail to aggregate but rather remain flattened and spatially separated from one another, suggeting that syndecan-3 antibodies impair the formation of precartilage condensations. These results indicate that syndecan-3 plays an important role in regulating the onset of limb chondrogenesis, perhaps by mediating the cell-cell and cell-matrix interactions required for condensation and subsequent cartilage differentiation.

Aggrecans↗
PubMed2004

Indian hedgehog and syndecans-3 coregulate chondrocyte proliferation and function during chick limb skeletogenesis.

Hedgehog proteins exert critical roles in embryogenesis and require heparan sulfate proteoglycans (HS-PGs) for action. Indian hedgehog (Ihh) is produced by prehypertrophic chondrocytes in developing long bones and regulates chondrocyte proliferation and other events, but it is not known whether it requires HS-PGs for function. Because the HS-PG syndecan-3 is preferentially expressed by proliferating chondrocytes, we tested whether it mediates Ihh action. Primary chick chondrocyte cultures were treated with recombinant Ihh (rIhh-N) in absence or presence of heparinase I or syndecan-3 neutralizing antibodies. While rIhh-N stimulated proliferation in control cultures, it failed to do so in heparinase- or antibody-treated cultures. In reciprocal gain-of-function studies, chondrocytes were made to overexpress syndecan-3 by an RCAS viral vector. Cells became more responsive to rIhh-N, but even this response was counteracted by heparinase or antibody treatment. To complement the in vitro data, RCAS viral particles were microinjected in day 4-5 chick wing buds and effects of syndecan-3 misexpression were monitored over time. Syndecan-3 misexpression led to widespread chondrocyte proliferation and, interestingly, broader expression and distribution of Ihh. In addition, the syndecan-3 misexpressing skeletal elements were short, remained cartilaginous, lacked osteogenesis, and exhibited a markedly reduced expression of collagen X and osteopontin, products characteristic of hypertrophic chondrocytes and bone cells. The data are the first to indicate that Ihh action in chondrocyte proliferation involves syndecan-3 and to identify a specific member of the syndecan family as mediator of hedgehog function.

Animals↗
PubMed2007

Regulated expression of syndecan-4 in rat calvaria osteoblasts induced by fibroblast growth factor-2.

Fibroblast growth factor-2 (FGF2) is a member of a prominent growth factor family that drives proliferation in a wide variety of cell types, including osteoblasts. The binding and signal transduction triggered by these mitogens is dependent on glycosaminoglycan (GAG) sugars, particularly of the heparan sulfate (HS) class. These are secreted in proteoglycan (PG) complexes, some of which become FGF co-receptors. The syndecans, the transmembrane forms of HSPG of which there are four members, act as multifunctional receptors for a variety of ligands involved in cell-extracellular matrix (ECM) adhesion as well as growth factor binding. To understand the role of syndecans in developing osteoblasts, the effects of exogenous FGF2 on syndecan expression were examined using primary rat calvarial osteoblasts. All four syndecan mRNAs were expressed in the osteoblasts, although only syndecan-4 was upregulated by FGF2 treatment in a dose-dependent manner. This upregulation could be abrogated by pretreatment with the protein synthesis inhibitor cycloheximide, suggesting that the upregulation of syndecan-4 by FGF2 is not a primary response. Osteoblast proliferation and mineralization were enhanced by exogenous FGF2 treatment, but could be specifically diminished by anti-syndecan-4 antibody pretreatment. This treatment also blocked FGF2-induced extracellular signal-regulated kinase activation, but not the expression of the bone-specific transcription factor Runx2. These results demonstrate that mitogen-triggered syndecan-4 expression is an intrinsic part of the pathways subtending osteoblast proliferation and mineralization.

Animals↗
PubMed2006

Immunological localization of syndecan-1 in human endometrium throughout the menstrual cycle.

OBJECTIVE: To examine the expression of syndecan-1 in the endometrium during the menstrual cycle. DESIGN: The expression of syndecan-1 was determined by tissue microarray and immunohistochemistry. SETTING: Academic clinical and research laboratories. PATIENT(S): Seventy-one regularly cycling women who underwent endometrial biopsy. INTERVENTION(S): Endometrial samples representing five stages of the menstrual cycle were used for the study. MAIN OUTCOME MEASURE(S): Semiquantitative analysis by evaluating the intensity of immunohistochemical reactivity of syndecan-1 by using a modified HSCORE. RESULT(S): Endometrial syndecan-1 was expressed in the luminal and glandular epithelium as well as in the stroma throughout the menstrual cycle in a nonsynchronized fashion. In the luminal epithelium, the expression of syndecan-1 was statistically significantly higher in the mid-secretory phase when compared with the proliferative phase. In the stroma, however, the expression of syndecan-1 was down-regulated after ovulation and remained at a low level through the secretory phases. Differences between the proliferative and mid secretory, as well as between the ovulatory and the early, mid, and late secretory phases, all were statistically significant. CONCLUSION(S): Syndecan-1 is up-regulated in luminal epithelial cells during the mid-secretory phase and is down-regulated in the stroma during the early to late secretory phases. The differential expression of syndecan-1 coincides with the endometrial remodeling throughout the menstrual cycle.

Adult↗
PubMed2006

The role of syndecans in disease and wound healing.

Syndecans are a family of transmembrane heparan sulfate proteoglycans widely expressed in both developing and adult tissues. Until recently, their role in pathogenesis was largely unexplored. In this review, we discuss the reported involvement of syndecans in human cancers, infectious diseases, obesity, wound healing and angiogenesis. In some cancers, syndecan expression has been shown to regulate tumor cell function (e.g. proliferation, adhesion, and motility) and serve as a prognostic marker for tumor progression and patient survival. The ectodomains and heparan sulfate glycosaminoglycan chains of syndecans can also act as receptors/co-receptors for some bacterial and viral pathogens, mediating infection. In addition, syndecans bind to obesity-related factors and regulate their signaling, in turn modulating food consumption and weight balance. In vivo animal models of tissue injury and in vitro data also implicate syndecans in processes necessary for wound healing, including fibroblast and endothelial proliferation, cell motility, angiogenesis, and extracellular matrix organization. These new insights into the involvement of syndecans in disease and tissue repair coupled with the emergence of syndecan-specific molecular tools may lead to novel therapies for a variety of human diseases.

Animals↗
PubMed2005

Stromal syndecan-1 expression is an adverse prognostic factor in oral carcinomas.

Syndecan-1, a transmembrane proteoglycan, may exert anti-proliferative effects and promote cell growth by binding various growth factors. Malignant epithelial cells often down-regulate their own syndecan-1 production, and are capable of inducing an aberrant syndecan-1 expression in stromal fibroid cells. Decreased tumor cell syndecan-1 levels in human head and neck squamous cell carcinomas indicate poor prognosis, however, no correlation between stromal syndecan-1 expression and clinical parameters has previously been established. By means of immunohistochemistry, we observed a decrease in tumor cell syndecan-1 reactivity in 33/39 oral carcinoma cases, the degree of which, however, correlated only weakly with the clinical outcome (p = 0.097). Conversely, stromal syndecan-1 positivity proved to be a significant risk factor of recurrence (Cox analysis, p = 0.03) and tumor-specific death (p = 0.023) within a 24-month period after operation. Taken together, stromal expression of syndecan-1 is a reliable factor of adverse prognosis in oral carcinomas.

Adult↗
PubMed2002

Cytoplasmic interactions of syndecan-4 orchestrate adhesion receptor and growth factor receptor signalling.

Syndecan-4 is a ubiquitous transmembrane proteoglycan that localizes to the focal adhesions of adherent cells and binds to a range of extracellular ligands, including growth factors and extracellular-matrix proteins. Engagement of syndecan-4 is essential for adhesion formation in cells adhering via certain integrins, and for cell proliferation and migration in response to growth factors. The cytoplasmic domain of syndecan-4 interacts with a number of signalling and structural proteins, and both extracellular and cytoplasmic domains are necessary for regulated activation of associated transmembrane receptors. PDZ domain-containing scaffold proteins (syntenin and CASK) bind to the C-terminus of the syndecan-4 cytoplasmic domain and co-ordinate clustering of receptors and connection to the actin cytoskeleton. Syndecan-4 also binds and activates protein kinase Calpha in the presence of phosphatidylinositol 4,5-bisphosphate, and regulates signalling by Rho-family GTPases and focal adhesion kinase. This review discusses the cytoplasmic interactions of syndecan-4 and how they affect cell behaviour as a consequence of the interaction with extracellular ligands. These conclusions also offer an insight into the role of syndecan-4 in vivo, and are consistent with phenotypes generated as a consequence of abnormal syndecan-4 expression in pathologies and gene disruption studies.

Actins↗