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 behavior. Our earlier observations suggested that disruption of the actin cytoskeleton results in the inhibition of phorbol ester-induced matrix metalloproteinase (MMP)-9 expression. In this study, to understand the role of protein tyrosine phosphatases in matrix metalloproteinase-9 expression, we treated glioblastoma cells with vanadate and phenylarsine oxide (PAO), which are inhibitors of protein tyrosine phosphatases. Vanadate and PAO inhibited expression of phorbol ester-induced MMP-9 as well as constitutive expression of matrix metalloproteinase-2 in a dose- and time-dependent fashion. An assay of the activity of phosphotyrosine phosphatase (PTPase) indicated that vanadate-treated cells had reduced PTPase activity compared with that of untreated controls. Vanadate and PAO also inhibited actin polymerization, cell spreading, migration, and invasion of glioma cells. Furthermore, elevated 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 migration and invasion of glioma cells by their effect on the cytoskeleton and inhibition of MMP expression.
Chintala
S K
SK
Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Kyritsis
A P
AP
Mohan
P M
PM
Mohanam
S
S
Sawaya
R
R
Gokslan
Z
Z
Yung
W K
WK
Steck
P
P
Uhm
J H
JH
Aggarwal
B B
BB
Rao
J S
JS
D000199:Actins / Q000187:drug effects*; D001152:Arsenicals / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects*; D003599:Cytoskeleton / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D010750:Phosphoproteins / Q000378:metabolism; D019000:Phosphotyrosine / Q000032:analysis; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014638:Vanadates / Q000494:pharmacology*
D000199:Actins; D001152:Arsenicals; D015815:Cell Adhesion Molecules; D004791:Enzyme Inhibitors; D010750:Phosphoproteins; C029341:oxophenylarsine; D019000:Phosphotyrosine; D014638:Vanadates; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D017027:Protein Tyrosine Phosphatases; D020782:Matrix Metalloproteinases; D013755:Tetradecanoylphorbol Acetate