ADAM15 overexpression in NIH3T3 cells enhances cell-cell interactions

ADAM15 is a member of the family of metalloprotease-disintegrins that have been shown to interact with integrins in an RGD- and non-RGD-dependent mann er. In the present study, we examined the effects of ADAM15 overexpression on cell-matrix and cell-cell interactions in NIH3T3 cells. Tetracycline-reg ulated ADAM15 overexpression in NIH3T3 cells leads to an inhibition of migr ation on a fibronectin-coated filter in a Boyden chamber assay and in a scr atch wound model. The effects of ADAM15 overexpression on cell migration ar e not due to changes in matrix attachment or to the lack of extracellular s ignal-regulated kinase signaling response to PDGF or fibronectin. However, a decrease in monolayer permeability with ADAM15 overexpression and altered cell morphology suggest a possible increase in cell-cell interaction. Anal ysis of adhesion of NIH3T3 cells to a polyclonal population of cells retrov irally transduced to overexpress ADAM15 demonstrates a 45% increase in cell adhesion, compared with enhanced green fluorescent protein-expressing cont rol cells. In addition, we demonstrate localization of HA-epitope-tagged AD AM15 to cell-cell contacts in an epithelial cell line that forms extensive cell-cell contact structures. Thus, overexpression. of ADAM15 in NIH3T3 cel ls appears to enhance cell-cell interactions, as suggested by decreased cel l migration, altered cell morphology at the wound edge, decreased monolayer permeability, and increased cell adhesion to monolayers of cells expressin g ADAM15 by retroviral transduction. (C) 2001 Academic Press.