Metalloproteinase expression in normal and malignant oral keratinocytes: stimulation of MMP-2 and -9 by scatter...

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• Matrix metalloproteinases (MMPs) are crucial for tissue remodelling, tumor invasion, and metastasis.
• Scatter factor (SF) is a fibroblast-secreted factor that affects epithelial cell adhesion, motility, and invasiveness via the c-met receptor.

Purpose of the Study:

• To investigate whether Scatter factor (SF) regulates the production of Matrix metalloproteinases (MMPs) by epithelial cells.
• To explore the role of SF in oral epithelial cell behavior relevant to wound healing and neoplasia.

Main Methods:

• Analysis of MMP production in oral squamous cell carcinoma cell lines, a human keratinocyte line (UP), and primary oral mucosal keratinocytes.
• Supernatants were analyzed using 0.1% gelatin zymography to detect MMP activity.
• MMPs were identified using human recombinant enzymes and specific inhibitors; c-Met receptor presence was confirmed.

Main Results:

• Oral mucosal keratinocytes, UP, and H357 cells expressed both MMP-2 and MMP-9; H376 cells expressed only MMP-2.
• SF significantly increased MMP-9 expression in UP cells and MMP-2 expression in H376 cells.
• Both MMP-2 and MMP-9 activity increased in H357 and normal keratinocyte supernatants upon SF stimulation, an effect blocked by an anti-SF antibody.

Conclusions:

• Scatter factor (SF) stimulates Matrix metalloproteinase (MMP) expression in various oral epithelial cells, including normal keratinocytes and cancer cell lines.
• SF signaling through the c-Met receptor plays a role in regulating oral keratinocyte behavior.
• SF-induced MMP modulation may be significant in oral wound healing and the development of oral neoplasia.