|Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Because microtubules are important components of cell motility and intracellular transport, it is reasonable to propose that an antimicrotubule agent, estramustine's depolymerizing effect on glioma microtubules would modulate cell invasicveness. To determine whrther 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 employed in this study. The zymogram revealed that an activated (62kD) form of Matrix Metalloproteinase-2 diminished with increasing eatramustine 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オM,compared with the control group. On the haptoinvasion assay, no statistically significant difference was seen in the 0.5オM estramustine group, while 1 to 10オM estramustine groups revealed significant suppression of invasion from 6 to 24 hours in a dode-dependent manner. The results syggest that estramustine suppresses the invasion of U87MG cells in vitro by the decreasing available matrix metalloproteinase-2, an affect caused by the disassembly of microtubules. Suppression of the infiltrative capacity of malignant glioma cells could be of significant value in the treafment of this disease.