Cloning of a novel membrane-linked metalloproteinase from human myeloma cells

McKie, Norman; Dallas, D. J.; Edwards, Tracy; Apperley, JF; Russell, R. G. G.; Croucher, Peter I.

doi:10.1042/bj3180459

Cited by 18 publications

(13 citation statements)

References 18 publications

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“…In addition, ADAM‐9 has been reported to be able to shed the ectodomain of membrane‐anchored heparin‐binding EGF‐like growth factor from Vero‐H cells (Izumi et al , 1998). Although it is unclear whether TACE or ADAM‐9 will process other membrane‐bound proteins, we have shown that myeloma cells express these, and other, members of the ADAM family (McKie et al , 1996 and unpublished observations). Syndecan‐1 shedding has been reported to be mediated by a TIMP‐3‐sensitive metalloproteinase in P3X63 cells, supporting a role for an ADAM‐like enzyme in this process (Fitzgerald et al , 2000).…”

Section: Discussionmentioning

confidence: 89%

Evidence of a role for a non‐matrix‐type metalloproteinase activity in the shedding of syndecan‐1 from human myeloma cells

2001

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Summary. Syndecan-1 is a cell surface proteoglycan that is expressed on human myeloma cells and is thought to act as a co-receptor for certain extracellular matrix proteins and growth factors. The ectodomain of syndecan-1 is thought to be shed from the surface of myeloma cells, although the exact mechanism of release remains unclear. In this study, we used a panel of inhibitors to identify the class of proteinase responsible for shedding the soluble syndecan-1 ectodomain from human myeloma cells. Using enzymelinked immunosorbent assay, flow cytometry and immunocytochemistry, we demonstrated that myeloma cell lines expressed syndecan-1 on their surface and that this was shed constitutively, but to a varying extent. In addition, phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, stimulated a marked loss of cell surface syndecan-1 from each of the cell lines and this was associated with a corresponding increase in soluble syndecan-1. Inhibitors of serine and cysteine proteinases, and matrix-type metalloproteinases, did not inhibit constitutive or PMA-stimulated syndecan-1 shedding from JJN3 and RPMI 8226 cells. However, BB-94, a hydroxamatebased, broad-spectrum, metalloproteinase inhibitor, substantially suppressed constitutive and PMA-stimulated syndecan-1 loss from myeloma cells. These data indicate that a non-matrix-type metalloproteinase is responsible for syndecan-1 shedding from the surface of myeloma cells.

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Section: Discussionmentioning

confidence: 89%

Evidence of a role for a non‐matrix‐type metalloproteinase activity in the shedding of syndecan‐1 from human myeloma cells

2001

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“…In this capacity, plasma cell MMP may play a crucial role in the connective tissue destruction in diseases such as RA and scleritis. Recently, McKie et al [32] cloned a novel 76-kDa membrane-associated MMP from human myeloma cells and suggested the potential involvement of this proteinase in the ECM degradation observed in multiple myeloma (a plasma cell neoplasm).…”

Section: Discussionmentioning

confidence: 98%

Expression of matrix metalloproteinases by human plasma cells and B lymphocytes

et al. 1998

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Matrix metalloproteinases (MMP) are proteolytic enzymes that play a key role in tissue remodelling during physiological and pathological processes, by initiating the degradation of extracellular matrix. MMP overexpression can lead to tissue destruction which is characteristic of chronic inflammatory diseases such as rheumatoid arthritis and scleritis. Plasma cells are often abundant at such sites of chronic inflammation. In the present study we investigated whether plasma cells could contribute to matrix degradation by their expression of MMP In situ hybridization and immunohistochemical analyses on diseased synovial and scleral tissue demonstrated the expression of stromelysin-1 (MMP-3) and gelatinase B (MMP-9), but little or no tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) mRNA, by IgG-positive plasma cells. Northern blot analysis of RNA extracted from a human plasma cell line (ARH-77), Epstein-Barr virus-transformed B cells, and purified peripheral blood B cells, demonstrated expression of stromelysin mRNA. TIMP-1 mRNA was only detected by the more sensitive reverse transcription PCR method in these cell types. Plasma cells and B lymphocytes cultured in the presence of monensin demonstrated cytoplasmic gelatinase B. Gelatin and casein zymography on conditioned media (CM) derived from cytokine treated plasma cells revealed the induction of secreted gelatinase and stromelysin activity. Western blotting confirmed the presence of stromelysin-1 and TIMP-1 proteins in plasma cell CM. These data suggest that plasma cells are not only capable of modulating an inflammatory response by antibody and cytokine production, but also by their ability to produce MMP. Secretion of MMP from focal aggregates of plasma cells may play a critical role in tissue destructive diseases such as rheumatoid synovitis and scleritis.

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“…The mechanism by which the soluble form of syndecan‐1 is generated is not fully clear. Syndecan‐1 may be shed from the surface of cells by proteases such as MMP‐9 and ADAM12 (a disintegrin and metalloprotease 12) or by non‐matrix‐type metalloproteinases (19–21).…”

Section: Discussionmentioning

confidence: 99%