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.
Kaushal
G P
GP
Department of Medicine, Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, Little Rock 72205-7199, USA.
Xiong
X
X
Athota
A B
AB
Rozypal
T L
TL
Sanderson
R D
RD
Kelly
T
T
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