Carbohydrate-mediated regulation of matrix metalloproteinase-2 activation in normal human fibroblasts and fibrosarcoma cells.
Matrix metalloproteinase-2 (MMP-2) is activated on the cell surface by membrane type 1-MMP (MT1-MMP). Activation of proMMP-2 is induced in vitro by concanavalin A (ConA). The regulation of proMMP-2 activation is, however, not yet fully understood. We investigated the effect of plant lectins, carbohydrates and inhibitors of the cytoskeleton on proMMP-2 activation in normal (HLF1) and malignant fibroblast (HT1080) cells. Native ConA induced proMMP-2 activation in both cell types while dimeric succinyl-ConA had no effect, suggesting that receptor clustering is involved in activation. Wheat germ agglutinin (WGA) also induced proMMP-2 activation. N-acetyl-D-glucosamine (GlcNac) inhibited the effects of ConA and WGA while mannose only inhibited ConA-induced proMMP-2 activation. Mannose also inhibited the expression of MT1-MMP mRNA induced by ConA. Cytochalasin B and colchicine had no effect on the ConA induction of proMMP-2 activation. These studies help to define some of the cellular and molecular mechanisms for the induction of proMMP-2 activation.
Gervasi
D C
DC
Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, USA.
Raz
A
A
Dehem
M
M
Yang
M
M
Kurkinen
M
M
Fridman
R
R
D000116:Acetylgalactosamine / Q000494:pharmacology; D000117:Acetylglucosamine / Q000494:pharmacology; D002241:Carbohydrates / Q000494:pharmacology*; D002460:Cell Line; D003078:Colchicine / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000378:metabolism; D005347:Fibroblasts; D005354:Fibrosarcoma; D018093:Gelatinases / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000494:pharmacology; D008168:Lung; D008358:Mannose / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D014407:Tumor Cells, Cultured
D002241:Carbohydrates; D004792:Enzyme Precursors; D037102:Lectins; D003208:Concanavalin A; D003571:Cytochalasin B; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase; D020778:Matrix Metalloproteinase 2; D000116:Acetylgalactosamine; D008358:Mannose; D003078:Colchicine; D000117:Acetylglucosamine