INDUCTION OF MATRIX METALLOPROTEINASE-9 REQUIRES A POLYMERIZED ACTIN CYTOSKELETON IN HUMAN-MALIGNANT GLIOMA-CELLS

Alterations in cytoskeleton and subsequent cell shape changes exert sp ecific effects on the expression of various genes. Our previous result s suggested that malignant human gliomas express elevated levels of ma trix metalloproteinases compared with normal brain tissue and low grad e gliomas. To understand the role of cell shape changes on matrix meta lloproteinase expression in human glioma cells, we treated SNB19 cells with cytochalasin-D, an inhibitor of actin polymerization, and colchi cine-B, a tubulin inhibitor, in the presence of phorbol 12-myristate 1 3-acetate. Cytochalasin-D treatment of SNB19 cells resulted in the los s of phorbol 12-myristate 13-acetate-induced matrix metalloproteinase- 9 (also known as gelatinase-B) expression and coincided with inhibitio n of actin polymerization, resulting in cell rounding. Moreover, compa red with monolayers, cells grown as spheroids or cell aggregates faile d to express matrix metalloproteinase-9 in the presence of phorbol 12- myristate 13-acetate. Matrix metalloproteinase-g expression was also i nhibited by calphostin-C, a protein kinase inhibitor, suggesting the i nvolvement of protein kinase C in matrix metalloproteinase-g expressio n. Phorbol 12-myristate 13-acetate-induced invasion of SNB19 cells thr ough 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 t he subsequent invasion of human glioma cells.