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 metalloproteinase (MMP) family, is considered to be a critical factor in tumor cell penetration of the extracellular matrix. To express catalytic activity, however, gelatinase A requires activation by another MMP, membrane type 1-matrix metalloproteinase (MT1-MMP). The head and neck squamous cell carcinoma cell line, UM-SCC-1, forms a quiescent monolayer atop collagen unless stimulated with epidermal growth factor (EGF; 3.5 nmol/L), which induces single cell invasion within 48 hours. To determine the role of the MT1-MMP/gelatinase A protease system in an in vitro stromal invasion model, expression vectors for MT1-MMP and gelatinase A were transfected into UM-SCC-1 (SCC-1/MT and SCC-1/gelA, respectively). SCC-1/MT tumor cells were found to invade in the absence of growth factor stimulation. Additionally, these cells displayed shorter onset to invasion and penetrated deeper into the collagen gel with EGF stimulation than did control vector transfectants. SCC-1/gelA cells similarly demonstrated invasion in the absence of EGF and a heightened invasive potential under EGF-stimulated conditions. These results suggest that the MT1-MMP/gelatinase A protease system participates in squamous cell carcinoma invasion of collagenous matrices.
Rosenthal
E L
EL
Department of Otolaryngology-Head and Neck Surgery, Division of Hematology/Oncology, University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, USA.
Hotary
K
K
Bradford
C
C
Weiss
S J
SJ
D001363:Awards and Prizes; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D004789:Enzyme Activation / Q000502:physiology; D004815:Epidermal Growth Factor / Q000502:physiology; D005109:Extracellular Matrix / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D020778:Matrix Metalloproteinase 2 / Q000502:physiology*; D020782:Matrix Metalloproteinases / Q000502:physiology*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D009361:Neoplasm Invasiveness; D010039:Otorhinolaryngologic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D004815:Epidermal Growth Factor; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2