Suppression of matrix metalloproteinase-2-mediated cell invasion in U87MG, human glioma cells by anti-microtubule agent: in vitro study.
Suppression of matrix metalloproteinase-2-mediated cell invasion in U87MG, human glioma cells by anti-microtubule agent: in vitro study.
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DOI：
10.1038/bjc.1998.4
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发表时间：
1998
影响因子：
8.8
通讯作者：
Teramoto, A
中科院分区：
文献类型：
--
作者：
Yoshida, D;Piepmeier, J M;Bergenheim, T;Henriksson, R;Teramoto, A
由于微管是细胞运动和细胞内运输的重要组成部分，这是合理的建议，解聚作用的抗微管剂，雌莫司汀，胶质瘤微管调节细胞的侵袭力。为了确定是否基质金属蛋白酶，在细胞侵袭的关键因素，暴露于雌莫司汀，细胞增殖试验，酶谱，胶原溶解试验和haptoinvasion试验的影响，在这项研究中使用。酶谱显示，激活（62 kDa）形式的基质金属蛋白酶-2减少雌莫司汀浓度的增加。胶原溶解试验表明，与对照组相比，雌莫司汀浓度为1、5和10 μ M时，雌莫司汀以剂量依赖性方式抑制酶活性的速率降低约2.5- 21倍。在接触侵袭测定中，在0.5 μ M雌莫司汀组中没有观察到统计学显著差异，而1-10 μ M雌莫司汀组显示从6至24小时以剂量依赖性方式显著抑制侵袭。结果表明，雌莫司汀抑制U87 MG细胞在体外的侵袭，通过减少可用的基质金属蛋白酶-2，微管解体引起的效果。抑制恶性胶质瘤细胞的浸润能力可能对该疾病的治疗具有重要价值。
Because microtubules are important components of cell motility and intracellular transport, it is reasonable to propose that the depolymerizing effect of an antimicrotubule agent, estramustine, on glioma microtubules would modulate cell invasiveness. To determine whether matrix metalloproteinases, key factors in cell invasion, are affected by exposure to estramustine, a cell proliferation assay, a zymogram, a collagenolysis assay and a haptoinvasion assay were used in this study. The zymogram revealed that an activated (62 kDa) form of matrix metalloproteinase-2 diminished with increasing estramustine concentrations. The collagenolysis assay demonstrated approximately 2.5- to 21-fold lower rates of enzymatic activity suppressed by estramustine in a dose-dependent manner at estramustine concentrations of 1, 5, and 10 microM, compared with the control group. On the haptoinvasion assay, no statistically significant difference was seen in the 0.5 microM estramustine group, whereas 1-10 microM estramustine groups revealed significant suppression of invasion from 6 to 24 h in a dose-dependent manner. The results suggest that estramustine suppresses the invasion of U87MG cells in vitro using the decreasing available matrix metalloproteinase-2, an effect caused by the disassembly of microtubules. Suppression of the infiltrative capacity of malignant glioma cells could be of significant value in the treatment of this disease.