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 v itro by concanavalin A (ConA). The regulation of proMMP2 activation is , however, not yet fully understood. We investigated the effect of pla nt 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 dim eric succinyl-ConA had no effect suggesting that receptor clustering i s involved in activation. Wheat germ agglutinin (WAG) also induced pro MMP-2 activation. N-acetyl-D-glucosamine (GlcNac) inhibited the effect s of ConA and WGA while mannose only inhibited ConA-induced proMMP-2 a ctivation. Mannose also inhibited the expression of MT1-MMP mRNA induc ed by ConA. Cytochalasin B and colchicine had no effect on the ConA in duction of proMMP-2 activation. These studies help to define some of t he cellular and molecular mechanisms for the induction of proMMP-2 act ivation. (C) 1996 Academic Press, Inc.