Membrane Type 1 Matrix Metalloproteinase Regulates Cellular Invasiveness and Survival in Cutaneous Epidermal Cells

Abstract

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.