Membrane type 1 matrix metalloproteinase regulates cellular invasiveness and survival in cutaneous epidermal cells.
Membrane type 1 matrix metalloproteinase is a member of the membrane-anchored matrix metalloproteinase family and is involved in tissue remodeling events ranging from tumor invasion and angiogenesis to growth and development. We sought to clarify the role of membrane type 1 matrix metalloproteinase in cutaneous epidermal cells using anti-sense cDNA expression in human keratinocytes. Modulation of membrane type 1 matrix metalloproteinase transcript and protein levels was achieved via retroviral expression of a 5' 1.4 kb anti-sense membrane type 1 matrix metalloproteinase construct and a 3.4 kb full-length sense membrane type 1 matrix metalloproteinase construct in primary and immortalized keratinocytes and SCC-25 cells. Maximal reductions were observed 48-72 h after transduction with 1.4 kb anti-sense membrane type 1 matrix metalloproteinase construct that correlated with significant decreased pro-matrix metalloproteinase-2 activation. Functionally, we found decreased cell migration, reduced cellular proliferation, and increased apoptotic nuclear fragmentation after 1.4 kb anti-sense membrane type 1 matrix metalloproteinase construct expression. Our findings suggest a role for membrane type 1 matrix metalloproteinase in human cutaneous epidermal cell invasion and survival mechanisms in vivo.
Nagavarapu
Usha
U
Department of Dermatology, Stanford University School of Medicine, The Molecular Medicine Research Institute, Sunnyvale, California 94085, USA.
Relloma
Kenneth
K
Herron
G Scott
GS
D016375:Antisense Elements (Genetics); D002455:Cell Division / Q000502:physiology; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003094:Collagen / Q000494:pharmacology; D053938:DNA Fragmentation / Q000502:physiology; D004792:Enzyme Precursors / Q000235:genetics; D000078404:Epidermal Cells; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000494:pharmacology; D018093:Gelatinases / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics* / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000235:genetics; D014161:Transduction, Genetic
D016375:Antisense Elements (Genetics); D004792:Enzyme Precursors; D005353:Fibronectins; D003094:Collagen; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase; D020781:Matrix Metalloproteinase 1