Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Syndecan-1 is a low-affinity receptor for basic fibroblast growth factor (bFGF). In this study, we used flow cytometry to examine expression of syndecan-1 on monoclonal cells from the blood (n = 37) and marrow (n = 81) of patients with plasma cell (PC) proliferative disorders (PCPD) and blood cells from patients (n = 39) with B cell chronic lymphocytic leukemia (B-CLL). The marrow CD38+CD45- and CD38+CD45+ PC were syndecan-1 positive in all patients with PCPD and there was no difference between patients with monoclonal gammopathy of undetermined significance (MGUS) vs multiple myeloma or cases with vs without bone lesions. In 38% of cases, syndecan-1 expression on the PC was heterogeneous with > or =25% of PC syndecan-1 negative. We found similar syndecan-1 expression on blood and marrow PC in the 36 cases with paired samples. CLL cells were syndecan-1 negative in 97% (38/39) of the cases. Syndecan-1 is a useful marker to detect malignant plasma cells in the blood or marrow; however, it is not helpful in distinguishing MGUS from active myeloma. In addition, syndecan-1 is present on the less mature (CD45+) PC, and there is heterogeneity of expression within and between patients. The relevance of the bFGF bound to myeloma cells via syndecan-1 remains to be elucidated.
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PMID:Syndecan-1 expression on malignant cells from the blood and marrow of patients with plasma cell proliferative disorders and B-cell chronic lymphocytic leukemia. 972 Jul 26

Syndecans have three highly conserved sites available for heparan sulfate attachment. To determine if all three sites are required for normal function, a series of mutated syndecans having two, one, or no heparan sulfate chains were expressed in ARH-77 cells. Previously, we demonstrated that expression of wild-type syndecan-1 on these myeloma cells mediates cell-matrix and cell-cell adhesion and inhibits cell invasion into collagen gels. Here we show that to optimally mediate each of these activities, all three sites of heparan sulfate attachment are required. Generally, an increasing loss of syndecan-1 function occurs as the number of heparan sulfate attachment sites decreases. This loss of function is not the result of a decrease in either the total amount of cell surface heparan sulfate or syndecan-1 core protein. In regard to cell invasion, cells expressing syndecan-1 bearing a single heparan sulfate attachment site exhibit a hierarchy of function based upon the position of the site within the core protein; the presence of an available attachment site at serine 47 confers the greatest level of activity, while serine 37 contributes little to syndecan-1 function. However, when all three heparan sulfate chains are present, significantly greater biological activity is observed than is predicted by the sum of the activities occurring when the chains act individually. This synergy provides a functional basis for the evolutionary conservation of the three heparan sulfate attachment sites on syndecans and supports the idea that molecular heterogeneity, which is characteristic of proteoglycans, contributes to their functional diversity.
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PMID:Multiple heparan sulfate chains are required for optimal syndecan-1 function. 979 16

ARH-77 human myeloma cells invade into type I collagen gels but become non-invasive when engineered to express syndecan-1, a heparan sulphate proteoglycan that promotes cell adhesion to collagen. To determine if syndecan-1 expression influences the activity of proteases that may facilitate invasion, we analysed media harvested from syndecan-1 expressing and non-expressing cells. High levels of a 92 kD gelatinase accumulated in serum-free growth medium of both parental and control-transfected ARH-77, but much less 92 kD gelatinase accumulated in the medium of ARH-77 transfectants expressing syndecan-1. The gelatinase was identified as matrix metalloproteinase (MMP)-9 because its activity was immunoprecipitated with a MMP-9-specific monoclonal antibody. Gelatinase activity and Western blot analyses revealed 2-3-fold less MMP-9 in medium from syndecan-1 transfected cells than in medium from parental cells. Decreased MMP-9 was not due to increased association of MMP-9 with cells expressing syndecan-1. An inverse correlation between the syndecan 1 level and the level of MMP-9 accumulation in the media was observed using a panel of ARH-77 transfectants expressing syndecan-1. Investigation of six unrelated human myeloma cell lines confirmed that high gelatinase levels were recovered from conditioned media of those that did not express syndecan-1 (ARH-77, Mer and Col) and one line that expressed a low level of syndecan-1 (RPMI-8226), but low gelatinase levels were recovered from media of lines that expressed high levels of syndecan-1 (ARK and clone 2+). Therefore syndecan-1 may play a dual role in inhibiting the metastasis of tumour cells by promoting cell adhesion to the extracellular matrix and suppressing the proteolytic activity needed for invasion.
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PMID:Syndecan-1 expression suppresses the level of myeloma matrix metalloproteinase-9. 1005 Jul 21

Syndecan-1, an important transmembrane heparan sulphate proteoglycan is expressed in distinct stages of differentiation of normal lymphoid cells: in pre-B cells and Ig-producing plasma cells; however, its normal function, or presence in lymphoid malignancies, is still largely unknown. The expression of syndecan-1 (CD138) was studied in 57 human non-Hodgkin lymphomas using immunocytochemistry and immunohistochemistry. Positive expression of syndecan-1 was found in the plasma cells in chronic lymphoblastic leukaemia (B-CLL) cases, in different plasmocytoid lymphomas as well as in myeloma. All normal and malignant Tcells, or CD5+ cells other than B-CLL proved to be negative. These results strongly suggest that syndecan-1 expression is a characteristic phenotypic marker for B-CLL and lymphoplasmocytoid lymphomas and could be used for diagnostic purposes.
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PMID:Syndecan-1 (CD138) expression in human non-Hodgkin lymphomas. 1093 Oct 10

Clinical features of multiple myeloma are linked with immunological phenotype of myeloma cells. The interactions between malignant plasma cells and proteins of ECM (extracellular matrix) or different cells results from the influence of adhesion molecules. In our study the expression of CD49b, CD49d, CD49e, CD49f on the myeloma cells has been estimated. These cells were obtained from bone marrow of 33 just diagnosed patients. Immunophenotyping was performed with flow cytometry method. Malignant plasma cells were identified by monoclonal antibody anti-CD138 (B-B4) directed against Syndecan-1. We have observed that in patients with high expression of laminin receptors CD49b, CD49f and lack of fibronectin receptors CD49d, CD49e more often renal failure has been confirmed.
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PMID:[The role of beta1 integrins in renal failure accompanied by multiple myeloma]. 1033 38

Syndecan-1 is a transmembrane proteoglycan expressed on the surface of tumor cells of various origins including myeloma, Hodgkin's disease, and certain human immunodeficiency virus (HIV) associated lymphomas. Functional studies in myeloma reveal that syndecan-1 may act as a multifunctional regulator of cell behavior in the tumor microenvironment; it mediates cell-cell adhesion, binding of myeloma cells to type I collagen, and inhibits tumor cell invasion into collagen gels. In addition, syndecan-1 is released from the surface of myeloma cells and this shed form of the molecule inhibits growth and induces apoptosis of myeloma cells and may modulate myeloma bone disease by inhibiting osteoclast formation and promoting osteoblast formation. In view of its effects on tumor cell growth, survival, adhesion and invasion and on bone cell differentiation, syndecan-1 may be an important potentially beneficial regulator of myeloma pathobiology. Further studies are needed to define the clinical significance of syndecan-1 in myeloma and to examine its functional significance in other lymphoid malignancies.
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PMID:Syndecan-1 (CD 138) in myeloma and lymphoid malignancies: a multifunctional regulator of cell behavior within the tumor microenvironment. 1035 Mar 30

Serum samples drawn at diagnosis from 174 myeloma patients were analyzed for the presence of the heparan [corrected] sulfate proteoglycan, syndecan-1. Syndecan-1 was elevated in 79% of patients (median, 643 units/mL) compared with 40 healthy controls (median, 128 units/mL), P <.0001. Serum syndecan-1 correlated with the following: serum creatinine, secretion of urine M-component over the course of 24 hours, soluble interleukin-6 (IL-6) receptor, C-terminal telopeptide of type I collagen, beta(2)-microglobulin, percentage of plasma cells in the bone marrow, disease stage, and serum M-component concentration. In order to evaluate syndecan-1 as a prognostic marker in multiple myeloma, it was entered into a multivariate Cox regression model. Data from 138 patients were available for this analysis. As a continuous variable, syndecan-1 was an independent prognostic parameter in addition to serum beta(2)-microglobulin and World Health Organization performance status. When syndecan-1 was dichotomized by the best cutoff (66th percentile, 1170 units/mL), the survival difference between the groups was highly significant: "high" syndecan-1 group had a median survival of 20 months, and the "low" syndecan-1 group had a median of 44 months (P <.0001). We conclude that syndecan-1 is a new independent prognostic parameter in multiple myeloma, and its role in prognostic classification systems should be further investigated. (Blood. 2000;95:388-392)
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PMID:Serum syndecan-1: a new independent prognostic marker in multiple myeloma. 1062 39

Plasmocyte selective monoclonal antibodies (MAb) recognizing syndecan-1 have recently been described. They belong to a new cluster, CD138. Using the MAb MI15, we investigated the expression of syndecan-1 in routinely paraffin-embedded tissues. Nontumoral lymph nodes (25 cases) and bone marrow biopsy specimens (63 cases) showed strong membrane staining of plasma cells only, allowing accurate analysis of the nuclear structure. The MI15 positivity correlated with kappa and lambda light chain expression in the cytoplasm. The percentages of plasma cells calculated in bone marrow biopsy specimens after MI15 staining were, respectively, 2.1% (range, 1% to 4%) in normal bone marrows, 8.5% (range, 5 to 17) in reactive plasmocytosis, and 4.66% in monoclonal gammapathy of undetermined significance (MGUS) patients (range, 1 to 13), in the same range but slightly higher than those obtained on smears or on hematoxylin and eosin (H&E)-stained sections. In multiple myeloma (40 cases), all plasma cell types were marked, and Mi15 MAb gave additional information in 8 of 40 (20%) patients. In lymph nodes, Mi15 MAb reacted with Reed-Sternberg cells of classical Hodgkin's disease in 23 of 31 cases (74%) with variable intensity. In contrast, nodular lymphocyte predominance Hodgkin's disease (10 cases), most B cell lymphomas (88 of 107 cases) and all T cell lymphomas (30 cases) were negative. In B cell lymphomas, plasmocytomas (8 cases), plasmocytic lymphomas (2 cases), and 5 of 13 cases of immunoblastic lymphoma with plasmocytoid differentiation were stained. In lymphoplasmocytoid lymphomas (4 lymph nodes and 20 bone marrow biopsy specimens), only mature plasma cells were positive. Moreover, a wide distribution of syndecan-1 was observed in normal and tumoral epithelial tissues. Finally, Mi15 MAb appears to be a reliable marker for identifying and quantifying normal and tumoral plasma cells in paraffin-embedded bone marrow and lymph node samples.
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PMID:The Mi15 monoclonal antibody (anti-syndecan-1) is a reliable marker for quantifying plasma cells in paraffin-embedded bone marrow biopsy specimens. 1066 16

Multiple myeloma is a deadly malignancy characterized by plasma cell infiltration of bones. The resulting effect is painful "punched-out" lesions where bone is eroded and filled with myeloma cells that suppress and replace the normal marrow components. Recently it has been shown that myeloma cells produce matrix-metalloproteinase-9 (MMP-9) and MMP-2 and that accumulation of MMP-9 protein is suppressed upon expression of the heparan sulfate proteoglycan, syndecan-1. In this review, we briefly consider the potential roles for MMPs in the pathogenesis of multiple myeloma. MMPs likely have major roles in: 1) the infiltration of bone and other tissues by the myeloma cells; 2) the osteolytic bone destruction caused by overly active osteoclasts, 3) extracellular matrix remodeling by bone marrow stromal cells; 4) promoting the invasion of the endothelial cells that form neoangiogenic blood vessels necessary to sustain tumor foci; and 5) promoting the growth of myeloma cells. Effective and safe synthetic inhibitors of MMPs are available and these may prove useful in limiting the growth and spread of myeloma cells. In addition, recent insights into the suppression of MMP-9 by syndecan-1 may suggest new strategies for treatment of myeloma.
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PMID:Matrix metalloproteinases in multiple myeloma. 1075 79

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.
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PMID:Syndecan-1 is targeted to the uropods of polarized myeloma cells where it promotes adhesion and sequesters heparin-binding proteins. 1100 7


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