Migration of epithelial cells through the basement membrane and underlying connective tissues are fundamental features of a range of processes includ- ing development, wound healing, cancer progres- sion, and metastasis. These involve alterations in cell-cell and cell-matrix interactions and the pro- duction of protease enzymes which degrade com- ponents of the surrounding extracellular matrix. There are four distinct categories of proteases: serine, cysteine and aspartyl proteinases and the matrix metalloproteinases (MMPs). The latter are a family of at least 20 Zn 2z -dependent matrix degrading enzymes (1) divided into categories on the basis of substrate speci®city. They include the interstitial collagenases (MMPs -1, -8 and -13), stromelysins (MMPs -3, -10 and -11), type IV collagenases (MMPs -2 and -9), membrane bound types or MT-MMPs, and other MMPs such as matrilysin or enamelysin (MMP-20) which are not readily classi®ed. Collectively, they have a broad spectrum of proteolytic activity and are capable of degrading all components of the extracellular matrix. Metalloproteinases are synthesised by both the epithelial and connective tissue cells of skin and oral mucosa, but the range and speci®city of those produced by a speci®c cell type under particular Metalloproteinase expression in normal and malignant oral keratinocytes: stimulation of MMP-2 and -9 by scatter factor Bennett JH, Morgan MJ, Whawell SA, Atkin P, Roblin P, Furness J, Speight PM. Metalloproteinase expression in normal and malignant oral keratinocytes: stimulation of MMP-2 and -9 by scatter factor. Eur J Oral Sci 2000; 108: 281±291. # Eur J Oral Sci, 2000 Matrix metalloproteinases (MMPs) are Zn 2z dependent proteases produced by a variety of cell types. They have a fundamental role in tissue remodelling, tumour invasion and metastasis. Scatter factor (SF), secreted by ®broblasts, has a paracrine action on epithelial cells and binds the trans-membrane c-met receptor inducing loss of adhesion, cell motility and invasiveness in vitro. The purpose of this study was to test if SF can regulate the production of MMPs by epithelial cells. Supernatants from oral squamous cell carcinoma-derived cells (H375 and H376), a human keratinocyte line (UP), and primary cultures of oral mucosal keratinocytes, grown in the presence or absence of SF, were analysed using 0.1% gelatin zymography. MMPs were characterised by comparison with human recombinant enzymes and by the use of speci®c inhibitors. Oral mucosal keratinocytes, UP, and H357 cells expressed MMP-2 and MMP-9, whilst H376 cells only expressed MMP-2. SF increased the expression of MMP-9 in UP and MMP-2 in H376 supernatants. Both MMP-2 and MMP-9 activity were increased in H357 and normal keratinocyte supernatants. This could be blocked using a human recombinant anti-SF antibody. In all epithelial lines tested, c-Met, the cell surface receptor for SF, could be detected. The results indicate that SF stimulates MMP expression in UP, H376, H357, and normal oral mucosal cells and points to a role for SF in the regulation of oral keratinocyte behaviour in wound healing and neoplasia. J. H. Bennett, M. J. Morgan , S. A. Whawell, P. Atkin, P. Roblin, J. Furness, P. M. Speight Department of Oral Pathology, Eastman Dental Institute for Oral Health Care Sciences, University College London, London, UK Dr. Jon Bennett, Department of Oral Pathology, Eastman Dental Institute for Oral Health Care Sciences, University College London, 256, Grays Inn Road, London WC1X 8LD, UK Telefax: z44±20±7915±1213 E-mail: j.bennett@eastman.ucl.ac.uk Key words: oral; keratinocyte; scatter factor; metalloproteinase; carcinoma Accepted for publication April 2000 Eur J Oral Sci 2000; 108: 281±291 Printed in UK. All rights reserved