Altered actin cytoskeleton and inhibition of matrix metalloproteinase expression by vanadate and phenylarsine oxide, inhibitors of phosphotyrosine phosphatases: Modulation of migration and invasion of human malignant glioma cells

Cell-matrix interactions exert a profound influence on cell function and be havior. Our earlier observations suggested that disruption of the actin cyt oskeleton results in the inhibition of phorbol ester-induced matrix metallo proteinase (MMP)-9 expression. In this study, to understand the role of pro tein tyrosine phosphatases in matrix metalloproteinase-9 expression, we tre ated glioblastoma cells with vanadate and phenylarsine oxide (PAO), which a re inhibitors of protein tyrosine phosphatases. Vanadate and PAO inhibited expression of phorbol ester-induced MMP-9 as well as constitutive expressio n of matrix metalloproteinase-2 in a dose- and time-dependent fashion. An a ssay of the activity of phosphotyrosine phosphatase (PTPase) indicated that vanadate-treated cells had reduced PTPase activity compared with that of u ntreated controls. Vanadate and PAO also inhibited actin polymerization, ce ll spreading, migration, and invasion of glioma cells. Furthermore, elevate d levels of protein tyrosine phosphorylation were observed in vanadate- and PAO-treated cells in both a concentration- and time-dependent fashion and were seen to have an inverse correlation with focal adhesion kinase protein expression. These results suggest that vanadate and PAO inhibited migratio n and invasion of glioma cells by their effect on the cytoskeleton and inhi bition of MMP expression. Mol. Carcinog. 26:274-285, 1999. (C) 1999 Wiley-L iss, Inc.