Induction of matrix metalloproteinase-9 requires a polymerized actin cytoskeleton in human malignant glioma cells
Induction of matrix metalloproteinase-9 requires a polymerized actin cytoskeleton in human malignant glioma cells
复制标题
DOI：
10.1074/jbc.273.22.13545
复制
发表时间：
1998-05-29
影响因子：
4.8
通讯作者：
Rao, JS
中科院分区：
文献类型：
--
作者：
Chintala, SK;Sawaya, R;Rao, JS
细胞骨架的改变和随后的细胞形状变化对各种基因的表达产生特定的影响。我们以前的研究结果表明，恶性人脑胶质瘤表达的基质金属蛋白酶水平升高与正常脑组织和低级别胶质瘤。为了了解细胞形状变化对人脑胶质瘤细胞基质金属蛋白酶表达的作用，我们在佛波醇12-肉豆蔻酸酯13-乙酸酯存在下，用细胞松弛素-D（一种肌动蛋白聚合抑制剂）和秋水仙素-B（一种微管蛋白抑制剂）处理SNB 19细胞。细胞松弛素-D处理SNB 19细胞导致佛波醇12-肉豆蔻酸酯13-乙酸酯诱导的基质金属蛋白酶-9（也称为明胶酶-B）表达的丧失，并与肌动蛋白聚合的抑制相一致，导致细胞变圆。此外，与单层细胞相比，生长为球状体或细胞聚集体的细胞在佛波醇12-肉豆蔻酸酯13-乙酸酯的存在下未能表达基质金属蛋白酶-9。基质金属蛋白酶-G的表达也被抑制钙蛋白酶-C，蛋白激酶抑制剂，表明蛋白激酶C参与基质金属蛋白酶-G的表达。细胞松弛素-D和钙磷蛋白-C可抑制佛波醇12-肉豆蔻酸酯13-乙酸酯诱导的SNB 19细胞通过Matrigel的侵袭。这些结果表明，肌动蛋白聚合转导的信号，调节基质金属蛋白酶-9的表达和随后的人类胶质瘤细胞的侵袭。
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-g expression was also inhibited by calphostin-C, a protein kinase inhibitor, suggesting the involvement of protein kinase C in matrix metalloproteinase-g 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.