
<ArticleTitle>Evidence of a role for a non-matrix-type metalloproteinase activity in the shedding of <prot>syndecan-1</prot> from human myeloma cells.</ArticleTitle>
<AbstractText><prot>Syndecan-1</prot> 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 <prot>syndecan-1</prot> 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 <prot>syndecan-1</prot> ectodomain from human myeloma cells. Using enzyme-linked immunosorbent assay, flow cytometry and immunocytochemistry, we demonstrated that myeloma cell lines expressed <prot>syndecan-1</prot> 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 <prot>protein kinase C</prot>, stimulated a marked loss of cell surface <prot>syndecan-1</prot> from each of the cell lines and this was associated with a corresponding increase in soluble <prot>syndecan-1</prot>. Inhibitors of serine and cysteine proteinases, and matrix-type metalloproteinases, did not inhibit constitutive or PMA-stimulated <prot>syndecan-1</prot> shedding from JJN3 and RPMI 8226 cells. However, BB-94, a hydroxamate-based, broad-spectrum, metalloproteinase inhibitor, substantially suppressed constitutive and PMA-stimulated <prot>syndecan-1</prot> loss from myeloma cells. These data indicate that a non-matrix-type metalloproteinase is responsible for <prot>syndecan-1</prot> shedding from the surface of myeloma cells.</AbstractText>
