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Evidence of a role for a non‐matrix‐type metalloproteinase activity in the shedding of syndecan‐1 from human myeloma cells
Author(s) -
Holen Ingunn,
Drury Noel L.,
Hargreaves Philip G.,
Croucher Peter I.
Publication year - 2001
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2001.02963.x
Subject(s) - syndecan 1 , ectodomain , cell culture , biology , matrix metalloproteinase , microbiology and biotechnology , metalloproteinase , cell , receptor , biochemistry , genetics
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 enzyme‐linked 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 hydroxamate‐based, 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.