Induction of matrix metalloproteinase-9 requires a polymerized actin cytoskeleton in human malignant glioma cells (Journal article)

Chintala, S. K./ Sawaya, R./ Aggarwal, B. B./ Majumder, S./ Giri, D. K./ Kyritsis, A. P./ Gokaslan, Z. L./ Rao, J. S.

Alterations in cytoskeleton and subsequent cell shape changes exert specific effects on the expression of various genes. Our previous results suggested that malignant human gliomas express elevated levels of matrix metalloproteinases compared with normal brain tissue and low grade gliomas. To understand the role of cell shape changes on matrix metalloproteinase expression in human glioma cells, we treated SNB19 cells with cytochalasin-D, an inhibitor of actin polymerization, and colchicine-B, a tubulin inhibitor, in the presence of phorbol 12-myristate 13-acetate. Cytochalasin-D treatment of SNB19 cells resulted in the loss of phorbol 12-myristate 13-acetate-induced matrix metalloproteinase-9 (also known as gelatinase-B) expression and coincided with inhibition of actin polymerization, resulting in cell rounding. Moreover, compared with monolayers, cells grown as spheroids or cell aggregates failed to express matrix metalloproteinase-9 in the presence of phorbol 12-myristate 13-acetate. Matrix metalloproteinase-9 expression was also inhibited by calphostin-C, a protein kinase inhibitor, suggesting the involvement of protein kinase C in matrix metalloproteinase-9 expression. Phorbol 12-myristate 13-acetate-induced invasion of SNB19 cells through Matrigel was inhibited by cytochalasin-D and calphostin-C. These results suggest that the actin polymerization transduces signals that modulate the expression of matrix metalloproteinase-9 expression and the subsequent invasion of human glioma cells.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: Actins/*metabolism,Biopolymers,Brain Neoplasms/*enzymology/pathology/ultrastructure,Cell Adhesion Molecules/metabolism,Collagenases/*biosynthesis,Cytochalasin D/pharmacology,Cytoskeleton/*metabolism,Enzyme Activation,Enzyme Induction,Enzyme Inhibitors/pharmacology,Focal Adhesion Kinase 1,Focal Adhesion Protein-Tyrosine Kinases,Glioma/*enzymology/pathology/ultrastructure,Humans,Matrix Metalloproteinase 9,NF-kappa B/metabolism,Neoplasm Invasiveness,Protein Kinase C/antagonists & inhibitors,Protein-Tyrosine Kinases/metabolism,Tetradecanoylphorbol Acetate/pharmacology,Tumor Cells, Cultured
ISSN: 0021-9258
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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