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

Shravan K. Chintala, Athanassios P. Kyritsis, Pamarthi M. Mohan, Sanjeeva Mohanam, Raymond Sawaya, Ziya Gokslan, W. K.Alfred Yung, Peter Steck, Joon H. Uhm, Bharat B. Aggarwal, Jasti S. Rao

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)274-285
Number of pages12
JournalMolecular Carcinogenesis
Volume26
Issue number4
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Protein Tyrosine Phosphatases
Vanadates
Matrix Metalloproteinases
Actin Cytoskeleton
Glioma
Matrix Metalloproteinase 9
Phorbol Esters
Focal Adhesion Protein-Tyrosine Kinases
Matrix Metalloproteinase 2
Glioblastoma
Cytoskeleton
Cell Communication
Polymerization
Cell Movement
Tyrosine
oxophenylarsine
Inhibition (Psychology)
Actins
Proteins
Phosphorylation

Keywords

  • Focal adhesion kinase
  • Matrix metalloproteinase-9
  • Phosphotyrosine phosphatase
  • Protease

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

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. / Chintala, Shravan K.; Kyritsis, Athanassios P.; Mohan, Pamarthi M.; Mohanam, Sanjeeva; Sawaya, Raymond; Gokslan, Ziya; Yung, W. K.Alfred; Steck, Peter; Uhm, Joon H.; Aggarwal, Bharat B.; Rao, Jasti S.

In: Molecular Carcinogenesis, Vol. 26, No. 4, 1999, p. 274-285.

Research output: Contribution to journalArticle

Chintala, Shravan K. ; Kyritsis, Athanassios P. ; Mohan, Pamarthi M. ; Mohanam, Sanjeeva ; Sawaya, Raymond ; Gokslan, Ziya ; Yung, W. K.Alfred ; Steck, Peter ; Uhm, Joon H. ; Aggarwal, Bharat B. ; Rao, Jasti S. / 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. In: Molecular Carcinogenesis. 1999 ; Vol. 26, No. 4. pp. 274-285.
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