Syndecan-1 expression suppresses the level of myeloma matrix metalloproteinase-9.
ARH-77 human myeloma cells invade into type I collagen gels but become non-invasive when engineered to express syndecan-1, a heparan sulphate proteoglycan that promotes cell adhesion to collagen. To determine if syndecan-1 expression influences the activity of proteases that may facilitate invasion, we analysed media harvested from syndecan-1 expressing and non-expressing cells. High levels of a 92 kD gelatinase accumulated in serum-free growth medium of both parental and control-transfected ARH-77, but much less 92 kD gelatinase accumulated in the medium of ARH-77 transfectants expressing syndecan-1. The gelatinase was identified as matrix metalloproteinase (MMP)-9 because its activity was immunoprecipitated with a MMP-9-specific monoclonal antibody. Gelatinase activity and Western blot analyses revealed 2-3-fold less MMP-9 in medium from syndecan-1 transfected cells than in medium from parental cells. Decreased MMP-9 was not due to increased association of MMP-9 with cells expressing syndecan-1. An inverse correlation between the syndecan 1 level and the level of MMP-9 accumulation in the media was observed using a panel of ARH-77 transfectants expressing syndecan-1. Investigation of six unrelated human myeloma cell lines confirmed that high gelatinase levels were recovered from conditioned media of those that did not express syndecan-1 (ARH-77, Mer and Col) and one line that expressed a low level of syndecan-1 (RPMI-8226), but low gelatinase levels were recovered from media of lines that expressed high levels of syndecan-1 (ARK and clone 2+). Therefore syndecan-1 may play a dual role in inhibiting the metastasis of tumour cells by promoting cell adhesion to the extracellular matrix and suppressing the proteolytic activity needed for invasion.
Department of Medicine, Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, Little Rock 72205-7199, USA.
G P
GP
Kaushal
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X
Xiong
A B
AB
Athota
T L
TL
Rozypal
R D
RD
Sanderson
T
T
Kelly
D017364:Collagenases / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D020780:Matrix Metalloproteinase 9; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009101:Multiple Myeloma / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D053668:Syndecan-1; D053667:Syndecans; D014407:Tumor Cells, Cultured
D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; D010450:Endopeptidases; D017364:Collagenases; D020780:Matrix Metalloproteinase 9