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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In multiple myeloma, malignant plasma cells are localized in marrow and rarely circulate in peripheral blood. To investigate the role of adhesion proteins in this process, we determined the expression and function of adhesion molecules on cell lines derived from patients with myeloma. The U266, ARH-77, IM-9, and HS-Sultan cell lines strongly expressed beta 1 and alpha 4 integrins (89% to 98% positive), confirming that VLA-4 is the principal integrin on these cell lines. The U266 and IM-9 cell lines also expressed alpha 3 integrin on 15% to 20% cells. In contrast, all lines lacked cell surface alpha 2, alpha 5, and alpha 6 integrin expression (< 5% positive). These cell lines adhered to fibronectin (20% to 40% specific binding), without significant binding to either collagen or laminin. Adhesion of these cell lines to fibronectin was partially blocked with either anti-beta 1 integrin monoclonal antibody (MoAb) (75% inhibition), anti-alpha 4 integrin MoAb (75% inhibition), or RGD peptide (50% inhibition), but was unaffected by anti-alpha v beta 3 or anti-alpha IIb beta 3 MoAbs. Moreover, the combination of anti-beta 1 plus RGD peptide or anti-alpha 4 plus RGD peptide inhibited binding to fibronectin by 80% and 95%, respectively. Finally, pretreatment and coculture of the IM-9 cell line with interleukin-6 (IL-6) resulted in a 52% decrease in specific binding to fibronectin (30% +/- 6% to 15% +/- 6%; P = .001), associated with a decrease in the number of cells expressing VLA-4 and a decrease in intensity of VLA-4 expression. These data suggest that myeloma cells adhere to fibronectin through VLA-4 as well as through RGD-dependent mechanisms, and that this binding can be downregulated by IL-6. Future studies of binding of both myeloma cell lines and freshly isolated tumor cells to extracellular matrix proteins and to marrow stroma may enhance our understanding of localization and trafficking of cells within the bone marrow microenvironment.
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PMID:Characterization of adhesion molecules on human myeloma cell lines. 142 1

Differentiating B lymphocytes undergo changes in cell-cell and cell-matrix adhesion that control their movement through a series of distinct microenvironments. The integral membrane proteoglycan, syndecan, is a candidate for mediating B lymphocyte-matrix interactions because it is expressed on B lymphocytes only at times when they associate with matrix, and because syndecan is known to behave as a matrix receptor on simple epithelia. However, syndecan from B lymphocytes is significantly smaller in molecular mass than syndecan from simple epithelia (85 vs 160 kDa) suggesting that syndecan may have distinct functions on these two cell types. Our study was undertaken to determine if syndecan mediates adhesion of B lineage cells to extracellular matrix. The murine myeloma cell line MPC-11 was used because syndecan is the only major heparan sulfate proteoglycan detected on these cells and because they express a form of syndecan almost identical to that found on normal B lymphocytes. Cell binding assays demonstrate that syndecan binds MPC-11 cells to type I collagen. Binding is inhibited by heparin, by pretreatment of cells with heparitinase or by growth of cells before the assay in chlorate, an inhibitor of sulfation. Solid phase assays show that syndecan purified from MPC-11 cells binds to type I collagen but not type IV collagen, laminin, or fibronectin. The interaction of MPC-11-derived syndecan with type I collagen is of relatively high affinity (Kd app = 143 nM) as measured by affinity coelectrophoresis. However, the 160-kDa form of syndecan isolated from epithelial cells has a greater than fourfold higher affinity for type I collagen (Kd app = 31 nM) than does the MPC-11 syndecan, suggesting that different molecular forms of syndecan have distinct ligand binding properties. These results demonstrate that syndecan can mediate B lymphocyte interactions with matrix and suggest that changes in syndecan expression during B cell differentiation are a mechanism for controlling B cell localization within specific microenvironments.
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PMID:Adhesion of B lymphoid (MPC-11) cells to type I collagen is mediated by integral membrane proteoglycan, syndecan. 160 36

Recently we reported the expression of the human natural killer cell associated antigen CD56 (Leu 19/NKH1) in plasma cells of a majority of multiple myeloma (MM) patients. CD56 is known to be an isoform of the human neural adhesion molecule N-CAM which is involved in homotypic adhesive interactions. By immunophenotyping using four CD56 specific monoclonal antibodies and immunoprecipitation analysis we here confirm that the Leu 19 antigen expressed by myeloma plasma cells is identical to N-CAM and corresponds to the 145 kDa isoform. Because of the possible biological role of adhesion molecules on myeloma cells, we compared the expression of N-CAM with the intercellular adhesion molecule 1 (ICAM-1) and the beta 1 and beta 2 integrins. By immunogold-silver staining of cytospin preparations of mononuclear cell suspensions, bone marrow plasma cells of 17 MM patients were analysed. Plasma cells expressed N-CAM (CD56) in 14 patients. ICAM-1 (CD54) in 16 patients, and beta 2 integrins (CD18) in eight patients. beta 1 integrins (CD29) were expressed in all patients. The expression of beta 2 integrins was always very weak while N-CAM, ICAM-1 and the beta 1 integrins showed a moderate to strong positivity. The plasma cells of five haematological normal individuals lacked significant N-CAM expression but were positive for ICAM-1 and both integrin subgroups. One plasma cell leukaemia patient and two out of four end-stage MM patients showed no expression of N-CAM or beta 2 integrins on their circulating plasma cells. Among 11 previously established myeloma cell lines, surface expression of ICAM-1 and the integrins was detected in most cases, while N-CAM was present in only four lines. Most cell lines showed coexpression of the fibronectin receptors (VLA-4 and VLA-5) and the laminin receptor (VLA-6). The collagen receptor (VLA-2) was not expressed. The N-CAM negative cell lines included four cell lines that were derived from plasma cell leukaemia patients. These results indicate that the expression of adhesion molecules is an intrinsic part of the biology of multiple myeloma.
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PMID:Expression of cytoadhesion molecules (CD56, CD54, CD18 and CD29) by myeloma plasma cells. 172 26

Fibronectin (FN) has been implicated in the formation of cryoprecipitates in rheumatic diseases and is present in tissues where, under pathological conditions, immune complexes are frequently deposited. We found elevated levels of FN in the plasma of 92% of multiple myeloma patients tested compared with a group of normal subjects, although the level of FN did not correlate with the level of the paraprotein. We then characterized the interacting fragments on both molecules and found that under physiological conditions of pH and ionic strength both heavy and light chain of all multiple myeloma and normal IgG showed affinity to FN; the active fragment on FN was found to be the aminoterminal heparin-binding domain. These findings raise the possibility that FN might be implicated in some of the clinical symptoms of multiple myeloma.
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PMID:High plasma fibronectin levels in multiple myeloma patients: possible mechanisms and clinical implications. 188 86

Monoclonal antibodies to chick type X collagen have been used to study the structure, biosynthesis, and location of type X in cartilage. The antibodies were produced by injecting purified type X collagen into female SJL/J mice and then fusing their spleen cells with Sp2/0 myeloma cells. Hybridoma culture supernatants were screened for antibodies to type X collagen by enzyme-linked immunosorbent assay and Western blots. Positive supernatants did not cross-react with other collagen types (I, II, IX, XI) or with fibronectin. Three monoclonal antibodies were chosen for further characterization. Two of them (1A6 and 6F6) recognize a pepsin-sensitive domain of type X collagen. Rotary shadowing showed that 1A6 and 6F6 both recognize the same end of type X, probably the aminoterminal non-triple helical domain. Amino acid sequencing of the intact protein and of the epitope-containing peptide confirmed that the antibody recognition sites for 1A6 and 6F6 are within the amino-terminal domain. Monoclonal antibody 2B3 reacts with the pepsinized (45 kDa) and weakly with the nonpepsinized (59 kDa) forms of type X collagen. The monoclonal antibodies were used for immunolocalization of type X in hypertrophic chondrocytes and reacted only with tissue samples from areas undergoing endochondral ossification, e.g. growth plate and fracture callus. Antibody 6F6, when coupled to Sepharose, selectively binds to type X collagen from cell and organ cultures. In a pulse-chase experiment, no processing of the 59-kDa form of type X could be detected. Two components with molecular masses of approximately 70 and 85 kDa, arising from a disulfide-bonded aggregate, were synthesized by both the permanent and calcifying cartilage organ cultures but did not react with the antibody, suggesting that these proteins are not related to type X. In summary, the pulse-chase results and the immune precipitation with monoclonal antibody 6F6 did not detect biosynthetic precursors larger than 59 kDa or proteolytically processed forms of type X.
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PMID:Monoclonal antibodies to type X collagen. Biosynthetic studies using an antibody to the amino-terminal domain. 282 50

In this study, large numbers of hybridomas (produced by syngeneic immunization with B16 mouse melanoma and fusion with NS-1 myeloma cells) were screened for the production of antibodies that affected morphology and growth of animal and human tumor cells in vitro. Two such antibodies, NORM-1 and NORM-2 (both IgG2a), inhibited the growth of B16 melanoma cells in soft agar and increased the serum requirements of tumor cells in tissue culture. Antibody NORM-2 also inhibited the growth of SV40-transformed 3T3 cells in agar and caused them to deposit more fibronectin into extracellular matrix. These antibodies thus seem to induce a more normal behavior of tumor cells in vitro. In vivo both antibodies reduced the number of growing lung tumors of B16 melanoma in C57BL/6 mice by 70%-90% when injected 3 days after the tumor cells. By immunoprecipitation of 35S-methionine-labeled cell extracts, NORM-2 antibody recognized a 59 kd protein in B16 mouse and in A375 human melanoma cells but not in 3T3 fibroblasts.
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PMID:Monoclonal antibodies NORM-1 and NORM-2 induce more normal behavior of tumor cells in vitro and reduce tumor growth in vivo. 298 98

Plasma fibronectin concentration was determined by electroimmunodiffusion and laser nephelometry in 40 healthy persons and 321 patients with myelo- and lymphoproliferative diseases and other malignancies. Decreased fibronectin concentrations were found in patients with leukemia, Hodgkin's and non-Hodgkin's lymphomas, myelofibrosis, polycythaemia rubra vera and angioimmunoblastic lymphadenopathy. Elevated fibronectin level was detected in patients with multiple myeloma. In patients with cancer of the lung, stomach and colon, fibronectin level was found in the normal range. Decreased fibronectin concentration was observed in patients with cancer of the breast and prostate. Lower plasma fibronectin concentrations were detected in all groups of patients with infectious septical complications as compared to the patients without infections.
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PMID:[Determination of plasma fibronectin in myeloproliferative and lymphoproliferative diseases and other malignancies]. 308 43

Plasma fibronectin has been implicated as an important determinant of neutrophil adhesion to plastic surfaces. Using a monoclonal antifibronectin antibody, we examined the role of fibronectin (Fn) in chemotactic factor-mediated neutrophil attachment to various substrates. The chemotactic factor N-formyl-methionyl-leucyl-phenylalanine (FMLP) significantly enhanced neutrophil adherence to multiple substrates including gelatin, gelatin coated with Fc fragments of human IgG or Fn, plastic alone, plastic coated with Fc fragments, or purified plasma Fn. An IgM monoclonal antibody to plasma Fn significantly inhibited FMLP-stimulated neutrophil attachment to gelatin, gelatin-Fc, gelatin-Fn, plastic, plastic-Fc, and plastic-Fn substrates when compared with the parent line myeloma supernatant or an irrelevant IgM monoclonal antibody. No reduction in FMLP-stimulated adherence to the gelatin-plasma or plastic-plasma substrates occurred in the presence of antibody. Anti-Fn antibody reduced FMLP-stimulated adhesion only when present during the entire assay; incubation of cells or substrates alone with antibody, followed by removal of excess antibody before addition of stimulus incubation, failed to alter adherence. These data suggest that neutrophil-derived Fn may play a role in chemotactic factor-induced neutrophil adherence to both collagenous and noncollagenous substrates. Further support for the hypothesis was suggested by the demonstration of release of immunoreactive Fn into incubation media from FMLP-stimulated neutrophils.
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PMID:Fibronectin mediates chemotactic factor-stimulated neutrophil substrate adhesion. 315 17

A monoclonal antibody, GTE52, was isolated from a fusion of myeloma cells with the lymphocytes of a mouse immunised with enzymatically dissociated guinea-pig trigeminal ganglion cells. GTE52 was found to stain the nuclei of satellite cells and Schwann cells, but not neurones, in the peripheral nervous system of guinea-pig and mouse. In the central nervous system GTE52 labelled glia and some neurones. Double-labelling experiments on primary cultures of optic nerve using antibodies to glial fibrillary acidic protein, galactocerebroside and fibronectin showed that GTE52 labelled a sub-population of astrocyte glia, possibly corresponding to the type 2 astrocytes, oligodendrocytes and not fibroblasts. Adult non-neural tissue was not stained by GTE52 with the exception of the smooth muscle of the gut. However, during development of the guinea-pig the antigen recognised by GTE52 was expressed in all cells of 16-day embryos but was lost from the tissues studied, which were not stained in the adult, from about embryonic day 60 onwards.
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PMID:A monoclonal antibody against a novel intracellular neural antigen expressed differentially in neural cell types. 354 5

Plasma fibronectin concentrations were studied in 10 patients with multiple myeloma. After plasma exchange for 3 d (2.5-3 l plasma daily) the plasma fibronectin decreased to about 50% of the initial level. Resynthesis of fibronectin seemed to increase during 3 d of plasmapheresis, and was sufficient to normalize plasma fibronectin concentration. The plasma fibronectin concentration reached the initial level within 2 d after interrupting plasmapheresis in spite of concurrent cytotoxic treatment. The patients studied showed no signs of infection.
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PMID:Plasma fibronectin levels during daily plasmapheresis. 358 4


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