THE METALLOPROTEINASE STROMELYSIN-1 (TRANSIN) MEDIATES PC12 CELL-GROWTH CONE INVASIVENESS THROUGH BASAL LAMINAE

Matrix metalloproteinases have been implicated in various extracellula r matrix remodeling events that occur during normal development and in a number of pathologies. In previous work with PC12 rat pheochromocyt oma cells, we found that the matrix metalloproteinase stromelysin-1 (S T1) was highly induced by nerve growth factor (NGF), but not by epider mal growth factor (EGF). Here, we show that ST1 immunoreactivity is pr esent in growth cones of NGF-treated PC12 cells, but not EGF-treated o r untreated cells. To determine whether ST1 expression confers neurite invasiveness, three lines of PC12 cells were produced that constituti vely express ST1 antisense mRNA. These lines expressed and secreted si gnificantly reduced levels of ST1 protein, as determined by immunoblot and immunocytochemical methods, but otherwise responded normally to N GF-treatment by elaborating neurites. We found, however, that the neur ites of these ST1 antisense cells showed a significantly reduced abili ty to penetrate a Matrigel reconstituted basal lamina, as compared to the parental cells, suggesting that ST1 confers neurite invasiveness. Finally, we show that ST1 is also expressed in vivo in sections throug h Embryonic Day 15 rat embryos, including neurons of both the peripher al and central nervous systems. These data indicate that ST1 may play a role in axonal growth in vivo, including a role in growth cone invas iveness. (C) 1995 Academic Press, Inc.