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Blood, 1 November 2000, Vol. 96, No. 9, pp. 3139-3146
NEOPLASIA
High levels of soluble syndecan-1 in myeloma-derived bone
marrow: modulation of hepatocyte growth factor activity
Carina Seidel,
Magne Børset,
Øyvind Hjertner,
Dianjun Cao,
Niels Abildgaard,
Henrik Hjorth-Hansen,
Ralph D. Sanderson,
Anders Waage, and
Anders Sundan
From the Institute of Cancer Research and
Molecular Biology, Norwegian University of Science and Technology,
Trondheim, Norway; the Department of Pathology, Arkansas Cancer
Research Center, Little Rock, AR; the Section of Hematology, Aarhus
University Hospital, Aarhus, Denmark; and the Section of Hematology,
Institute of Environmental Medicine, University Hospital, Trondheim,
Norway.
Syndecan-1 is a heparan sulfate proteoglycan expressed on the
surface of, and actively shed by, myeloma cells. Hepatocyte growth
factor (HGF) is a cytokine produced by myeloma cells. Previous studies
have demonstrated elevated levels of syndecan-1 and HGF in the serum of
patients with myeloma, both of negative prognostic value for the
disease. Here we show that the median concentrations of syndecan-1 (900 ng/mL) and HGF (6 ng/mL) in the marrow compartment of patients with
myeloma are highly elevated compared with healthy controls and controls
with other diseases. We show that syndecan-1 isolated from the marrow
of patients with myeloma seems to exist in an intact form, with
glucosaminoglycan chains. Because HGF is a heparan-sulfate binding
cytokine, we examined whether it interacted with soluble syndecan-1. In
supernatants from myeloma cells in culture as well as in pleural
effusions from patients with myeloma, HGF existed in a complex with
soluble syndecan-1. Washing myeloma cells with purified soluble
syndecan-1 could effectively displace HGF from the cell surface,
suggesting that soluble syndecan-1 can act as a carrier for HGF in
vivo. Finally, using a sensitive HGF bioassay (interleukin-11
production from the osteosarcoma cell line Saos-2) and intact
syndecan-1 isolated from the U-266 myeloma cell line, we found that the
presence of high concentrations of syndecan-1 (more than 3 µg/mL)
inhibited the HGF effect, whereas lower concentrations potentiated it.
HGF is only one of several heparin-binding cytokines associated with
myeloma. These data indicate that soluble syndecan-1 may participate in
the pathology of myeloma by modulating cytokine activity within the
bone marrow.
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