Role of membrane type 1-matrix metalloproteinase and gelatinase A in head and neck squamous cell carcinoma invasion in vitro

The proteolytic activity of gelatinase A, a member of the matrix metallopro teinase (MMP) family, is considered to be a critical factor in tumor cell p enetration of the extracellular matrix. To express catalytic activity, howe ver, gelatinase A requires activation by another MMP, membrane type 1-matri x metalloproteinase (MT1-MMP). The head and neck squamous cell carcinoma ce ll line, UM-SCC-1, forms a quiescent monolayer atop collagen unless stimula ted with epidermal growth factor (EGF; 3.5 nmol/L), which induces single ce ll invasion within 48 hours. To determine the role of the MT1-MMP/gelatinas e A protease system in an in vitro stromal invasion model, expression vecto rs for MT1-MMP and gelatinase A were transfected into UM-SCC-1 (SCC-1/MT an d SCC-1/gelA, respectively). SCC-1/MT tumor cells were found to invade in t he absence of growth factor stimulation. Additionally, these cells displaye d shorter onset to invasion and penetrated deeper into the collagen gel wit h EGF stimulation than did control vector transfectants. SCC-1/gelA cells s imilarly demonstrated invasion in the absence of EGF and a heightened invas ive potential under EGF-stimulated conditions. These results suggest that t he MT1-MMP/gelatinase A protease system participates in squamous cell carci noma invasion of collagenous matrices.