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)

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

Interaction with stromal cells is known to be crucial for growth and differentiation of hematopoietic cells. To characterize adhesion molecules involved in this interaction, we examined adhesion of a panel of lymphoid, myeloid, and mast cell lines with stromal cells. We found that very late antigen-4 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) were major adhesion molecules in lymphoid and myeloid cells, whereas myeloma cells adhered to stromal cells through hyaluronate. We investigated regulation of VLA-4 during differentiation of myeloid cells using a neutrophil precursor cell line, L-G3. Differentiation of neutrophils induced by granulocyte colony-stimulating factor was accompanied with down-regulation of VLA-4. Induced L-G3 cells adhered to stromal cells in proportion to the expression of VLA-4. Mast cells used two mechanisms to adhere to fibroblasts and stromal cells. They adhered to fibronectin through VLA-5 when stimulated with steel factor and also directly to membrane-anchored steel factor through c-kit.
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PMID:Adhesion molecules in hematopoietic cells. 752 78

The expression pattern of beta 1 integrin on the surface of tumor cells in patients with multiple myeloma (MM) is reviewed and compared with that of other B cell malignancies. The expression pattern of beta 1 integrin of plasma cells of healthy individuals was also compared with that of malignancies of plasma cells. Normal immature CD10+ B cell precursors in bone marrow are alpha 4+ and alpha 5+, while mature peripheral B cells are alpha 4+ and alpha 5+. In contrast to mature peripheral B cells, it is reported that plasma cells are alpha 4+ and alpha 5+. There are three points following in the phenotype characteristic of MM cells; (i) MM cells are alpha 4 strong positive, (ii) MM cells are beta 1 strong positive and (iii) MM cells are alpha 6strong positive. Because alpha 6+ cell lines of malignant plasma cells showed spread and chemotaxis on stimulation with laminin, alpha 6 beta 1 integrin might contribute of MM cells to transit laminin rich basement membrane of blood vessel to exit to the extravascular space. The difference of the phenotype between plasma cells and MM cells is the expression of alpha 5; plasma cells express alpha 5, but MM cells are lost in one half of the cases. The functional role of VLA-5 in MM cells is reviewed.
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PMID:[The expression pattern of adhesion molecules and their role of the tumor cells in patients with multiple myeloma]. 753 66

In order to evaluate putative changes of major adhesion molecule expression on plasma cells (PCs) associated with malignant transformation, tumor spreading, and immortalization, we have quantified and compared the expression of CD56, CD44, CD11a, CD49e, and CD45 RO/RA on normal PCs, malignant PCs from multiple myeloma patients in chronic phase, in accelerated phase with or without extramedullary progression, and from human myeloma cell lines. Plasma cell phenotype was defined with the use of two-color immunofluorescence in combination with B-B4 or anti-CD38 antibodies. We found that all the adhesion antigens were expressed on normal PCs. Malignancy was characterized by an overexpression of CD56, whereas extramedullary spreading was associated with a dramatic down expression of CD56. Although CD44 remained unchanged, the subpopulation of PCs expressing CD11a, CD49e, and CD45RA/RO were significantly reduced during malignancy, and each of these negative subpopulations increased during disease acceleration. We demonstrated that CD11a and CD49e expression were correlated and defined the same subpopulation of PCs. The phenotype of HMCLs was similar to the expression profile of patients in accelerated phase with extramedullary spreading. In conclusion, we show that significant changes of PC phenotype were associated with malignancy, were correlated with the disease evolution, and could be of diagnostic and prognostic value in individuals with monoclonal gammopathy and patients with multiple myeloma.
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PMID:Adhesion molecules on human myeloma cells: significant changes in expression related to malignancy, tumor spreading, and immortalization. 754 19

Heterogenous biological character of myeloma cells was associated with different expression of adhesion molecules. Myeloma cells could be phenotypically divided into two subpopulations: CD38++/VLA5+/MPC-1+(VLA-5+) cells and CD38++/VLA5-/MPC-1-(VLA-5-) cells. VLA-5- myeloma cells were morphologically immature and proliferated markedly with response to IL-6 in vitro, while VLA-5+ cells showed very low uptakes of 3H-TdR but secreted higher amounts of M-protein in vitro. These results suggest VLA-5- cells are proliferative precursor in myeloma. With respect to VLA-5 and MPC-1 expression, myeloma precursor cells (CD38++/VLA-5-/MPC-1-/CD10-/CD24-) showed similar phenotype to germinal center B cells (CD38+/VLA-5-/MPC-1-/CD10+/CD24-), rather than that of pre-B cells in the bone marrow (CD38+/VLA-5+/MPC-1-/CD10+/CD24+). Identification of precursor cells and characterization of their growth is important for the understanding of pathophysiology of myeloma and the therapeutic strategy.
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PMID:[Myeloma precursor cells]. 768 32

Recently, differentiation pathway of plasma cells from germinal center B cells has been clarified in detail. Most of bone marrow plasma cells are considered to be derived from germinal center B cells. Early plasma cells are detected in the peripheral blood, and in the bone marrow, immature, intermediate and mature plasma cells are identified by expression of adhesion molecules such as VLA-5 and MPC-1. Myeloma cells are also subclassified into immature, intermediate and mature myeloma cells. Immature myeloma cells can respond to interleukin 6 (IL-6) to proliferate, and circulate in the peripheral blood and markedly expand in relapse. Therefore, immature myeloma cells are considered to be clonogenic cells for myeloma, so-called myeloma precursor cells.
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PMID:[Myeloma precursor cells and their differentiation]. 769 84

Recent 2-color phenotypic analysis using anti-CD38 antibody reveals that plasma cells alone locate at CD38strong positive (CD38++) fraction and expression of adhesion molecules such as VLA-5 and MPC-1 can define VLA-5-MPC-1- immature, VLA-5-MPC-1+ intermediate and VLA-5+ MPC-1+ mature plasma (myeloma) cells. Furthermore, phenotypic analysis of plasma cells with anti-CD19 and -CD56 antibodies can distinguish normal (polyclonal) plasma cells from malignant (monoclonal) plasma cells; normal plasma cells from various tissues are all CD19+ CD56-, while malignant plasma cells are mostly CD19- CD56+. Therefore, this 2-color phenotypic analysis is very useful for differential diagnosis of bone marrow plasmacytosis, that is, myeloma, benign monoclonal gammopathy or polyclonal gammopathy, and furthermore contributes to understanding of differentiated stages of myeloma cells (immature, intermediate or mature myeloma cells).
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PMID:[Phenotypic analysis of myeloma cells]. 769 88

Long-term bone marrow cultures (LTBMC) from patients with multiple myeloma (MM) and normal donors were analyzed for immunophenotype and cytokine production. Both LTBMC adherent cells from myeloma and normal donor origin expressed CD10, CD13, the adhesion molecules CD44, CD54, vascular cell adhesion molecule 1, very late antigen 2 (VLA-2), and VLA-5, and were positive for extracellular matrix components fibronectin, laminin, and collagen types 3 and 4. LTBMC from myeloma patients and normal donors spontaneously secreted interleukin-6 (IL-6). However, levels of IL-6 correlated with the stage of disease; highest levels of IL-6 were found in LTBMC from patients with active myeloma. To identify the origin of IL-6 production, LTBMC from MM patients and normal donors were cocultured with BM-derived myeloma cells and cells from myeloma cell lines. IL-6 was induced by plasma cell lines that adhered to LTBMC such as ARH-77 and RPMI-8226, but not by nonadhering cell lines U266 and FRAVEL. Myeloma cells strongly stimulated IL-6 secretion in cocultures with LTBMC adherent cells from normal donors and myeloma patients. When direct cellular contact between LTBMC and plasma cells was prevented by tissue-culture inserts, no IL-6 production was induced. This implies that intimate cell-cell contact is a prerequisite for IL-6 induction. Binding of purified myeloma cells to LTBMC adherent cells was partly inhibited by monoclonal antibodies against adhesion molecules VLA-4, CD44, and lymphocyte function-associated antigen 1 (LFA-1) present on the plasma cell. Antibodies against VLA-4, CD29, and LFA-1 also inhibited the induced IL-6 secretion in plasma cell-LTBMC cocultures. In situ hybridization studies performed before and after coculture with plasma cells indicated that LTBMC adherent cells produce the IL-6. These results suggest that the high levels of IL-6 found in LTBMC of MM patients with active disease are a reflection of their previous contact with tumor cells in vivo. These results provide a new perspective on tumor growth in MM and emphasize the importance of plasma cell-LTBMC interaction in the pathophysiology of MM.
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PMID:Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term bone marrow cultures. 791 45

Multiple myeloma is characterized by the presence of malignant plasma cells predominantly localized in bone marrow. Our prior studies have suggested that human myeloma derived-cell lines adhere specifically to fibronectin and to bone marrow stromal cells (BMSCs) via beta 1 and beta 2 integrins as well as RGD peptide, and that tumour cell to BMSC contact triggers interleukin-6 (IL-6) secretion from BMSCs. Since IL-6 is a growth factor for myeloma, adhesion may be important in paracrine IL-6 mediated tumour cell growth. We therefore examined phenotypic expression of adhesion molecules on the U266 and IM-9 human myeloma-derived cell lines using the panel of monoclonal antibodies (MoAbs) directed at adhesion molecules submitted to the Vth International Conference on Human Leukocyte Differentiation Antigens. U266 and IM-9 myeloma cell lines express mainly CD29, CD49d, VLA-1, CD18, CD54, ICAM-2 and ICAM-3. In contrast, CD49b, VLA-3, CD49f, CD11b, VCAM-1, selectins and selectin-ligands were not expressed on these cell lines. Specific adherence of IM-9 cells to BMSC line LP101 was demonstrated which could be partially blocked by pre-incubation and culture of tumour cells with anti-beta 1 integrin, anti-beta 2 integrin, anti-CD49d, anti-VLA-5, anti-CD11a, anti-CD44 and anti-CD54 MoAbs. The combination of these MoAbs (anti-CD29, CD18, CD11a, CD49d, VLA-5, CD44, CD54, ICAM-2, ICAM-3 MoAbs) decreased but did not completely abrogate binding of IM-9 to BMSCs. Moreover, increases in IL-6 secretion from BMSCs after adherence of IM-9 cells were also partially blocked by these MoAbs. These findings suggest that multiple adhesion pathways may mediate adherence of myeloma cell lines to BMSCs, localizing tumour cells in the marrow microenvironment and triggering IL-6 secretion by BMSCs which may augment tumour cell growth.
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PMID:Cell surface expression and functional significance of adhesion molecules on human myeloma-derived cell lines. 799 88

We report a novel, reproducible methodology which enabled 10 human myeloma cell lines (HMCL) to be obtained from each of 10 tumor samples harvested from 9 patients with extramedullary proliferation. Fresh samples were cultured with interleukin 6 (IL-6) and granulocyte macrophage-colony stimulating factor (GM-CSF) at a high cell density and resulting HMCL growth became progressively dependent on IL-6 alone, no longer requiring GM-CSF. These HMCL, which had the same immunoglobulin gene rearrangements as the patients' original myeloma cells, were designated XG-1 to XG-9. XG HMCL had a plasma cell morphology, expressed plasma cell antigen (Ag), namely cytoplasmic immunoglobulins, CD38, B-B4 Ag, and CD77, and lacked the usual B-cell Ag. They also expressed activation antigens such as CD28 with coexpression of CD28 and its ligand, B7 Ag, in four HMCL. Six HMCL expressed CD40, 4 CD23, and 5 its ligand, CD21. The XG HMCL bore adhesion molecules VLA-4 and CD44 (all 10 HMCL), VLA-5 (7 HMCL), and CD56 (4 HMCL). Finally, cytogenetic study of 8 HMCL indicated a 14q+ chromosome, and t(11,14) translocation was found in 6 of 8 and 5 of 8 HMCL, respectively. The possibility of obtaining malignant plasma cell lines reproducibly from each patient with extramedullary proliferation offers a unique tool for studying the phenotype and abnormalities of the still unidentified tumor stem cell in this disease.
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PMID:Reproducible obtaining of human myeloma cell lines as a model for tumor stem cell study in human multiple myeloma. 820 90


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